TY - JOUR A1 - Beckmann, Nadine A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Gulbins, Erich A1 - Nomellini, Vanessa A1 - Caldwell, Charles C. T1 - Burn injury impairs neutrophil chemotaxis through increased ceramide JF - Shock : injury, inflammation, and sepsis, laboratory and clinical approaches N2 - Infection is a common and often deadly complication after burn injury. A major underlying factor is burn-induced immune dysfunction, particularly with respect to neutrophils as the primary responders to infection. Temporally after murine scald injury, we demonstrate impaired bone marrow neutrophil chemotaxis toward CXCL1 ex vivo. Additionally, we observed a reduced recruitment of neutrophils to the peritoneal after elicitation 7 days after injury. We demonstrate that neutrophil ceramide levels increase after burn injury, and this is associated with decreased expression of CXCR2 and blunted chemotaxis. A major signaling event upon CXCR2 activation is Akt phosphorylation and this was reduced when ceramide was elevated. In contrast, PTEN levels were elevated and PTEN-inhibition elevated phospho-Akt levels and mitigated the burn-induced neutrophil chemotaxis defect. Altogether, this study identifies a newly described pathway of ceramide-mediated suppression of neutrophil chemotaxis after burn injury and introduces potential targets to mitigate this defect and reduce infection-related morbidity and mortality after burn. KW - Acid sphingomyelinase KW - Akt KW - burn injury KW - ceramide KW - CXCR2 KW - immune KW - dysfunction KW - neutrophil chemotaxis KW - PTEN Y1 - 2021 U6 - https://doi.org/10.1097/SHK.0000000000001693 SN - 1073-2322 SN - 1540-0514 VL - 56 IS - 1 SP - 125 EP - 132 PB - Lippincott Williams & Wilkins CY - Hagerstown, Md. ER - TY - JOUR A1 - Seidel-Jacobs, Esther A1 - Kohl, Fiona A1 - Tamayo, Miguel A1 - Rosenbauer, Joachim A1 - Schulze, Matthias Bernd A1 - Kuss, Oliver A1 - Rathmann, Wolfgang T1 - Impact of applying a diabetes risk score in primary care on change in physical activity BT - a pragmatic cluster randomised trial JF - Acta diabetologica N2 - Aim There is little evidence of the impact of diabetes risk scores on individual diabetes risk factors, motivation for behaviour changes and mental health. The aim of this study was to investigate the effect of applying a noninvasive diabetes risk score in primary care as component of routine health checks on physical activity and secondary outcomes. Methods Cluster randomised trial, in which primary care physicians (PCPs), randomised (1:1) by minimisation, enrolled participants with statutory health insurance without known diabetes, >= 35 years of age with a body mass index >= 27.0 kg/m(2). The German Diabetes Risk Score was applied as add-on to the standard routine health check, conducted in the controls. Primary outcome was the difference in participants' physical activity (International Physical Activity Questionnaire) after 12 months. Secondary outcomes included body mass index, perceived health, anxiety, depression, and motivation for lifestyle change. Analysis was by intention-to-treat principle using mixed models. Results 36 PCPs were randomised; remaining 30 PCPs (intervention: n = 16; control: n = 14) recruited 315 participants (intervention: n = 153; controls: n = 162). A slight increase in physical activity was observed in the intervention group with an adjusted mean change of 388 (95% confidence interval: - 235; 1011) metabolic equivalents minutes per week. There were no relevant changes in secondary outcomes. Conclusions The application of a noninvasive diabetes risk score alone is not effective in promoting physical activity in primary care. Clinical Trial Registration: ClinicalTrials.gov (NCT03234322, registration date: July 31, 2017). KW - Risk score KW - Risk prediction model KW - Type 2 diabetes KW - Prevention KW - Physical activity KW - Primary care Y1 - 2022 U6 - https://doi.org/10.1007/s00592-022-01895-y SN - 0940-5429 SN - 1432-5233 VL - 59 IS - 8 SP - 1031 EP - 1040 PB - Springer CY - Mailand ER - TY - JOUR A1 - Solovyev, Nikolay A1 - Drobyshev, Evgenii A1 - Blume, Bastian A1 - Michalke, Bernhard T1 - Selenium at the neural barriers BT - a review JF - Frontiers in neuroscience / Frontiers Research Foundation N2 - Selenium (Se) is known to contribute to several vital physiological functions in mammals: antioxidant defense, fertility, thyroid hormone metabolism, and immune response. Growing evidence indicates the crucial role of Se and Se-containing selenoproteins in the brain and brain function. As for the other essential trace elements, dietary Se needs to reach effective concentrations in the central nervous system (CNS) to exert its functions. To do so, Se-species have to cross the blood-brain barrier (BBB) and/or blood-cerebrospinal fluid barrier (BCB) of the choroid plexus. The main interface between the general circulation of the body and the CNS is the BBB. Endothelial cells of brain capillaries forming the so-called tight junctions are the primary anatomic units of the BBB, mainly responsible for barrier function. The current review focuses on Se transport to the brain, primarily including selenoprotein P/low-density lipoprotein receptor-related protein 8 (LRP8, also known as apolipoprotein E receptor-2) dependent pathway, and supplementary transport routes of Se into the brain via low molecular weight Se-species. Additionally, the potential role of Se and selenoproteins in the BBB, BCB, and neurovascular unit (NVU) is discussed. Finally, the perspectives regarding investigating the role of Se and selenoproteins in the gut-brain axis are outlined. KW - selenium KW - selenoprotein P KW - low molecular weight selenium species KW - blood– cerebrospinal fluid barrier KW - blood– brain barrier KW - selenium transport KW - brain-gut axis KW - LRP8 Y1 - 2021 U6 - https://doi.org/10.3389/fnins.2021.630016 SN - 1662-453X VL - 15 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Hoffmann, Holger A1 - Ott, Christiane A1 - Raupbach, Jana A1 - Andernach, Lars A1 - Renz, Matthias A1 - Grune, Tilman A1 - Hanschen, Franziska S. T1 - Assessing bioavailability and bioactivity of 4-Hydroxythiazolidine-2-Thiones, newly discovered glucosinolate degradation products formed during domestic boiling of cabbage JF - Frontiers in nutrition N2 - Glucosinolates are plant secondary metabolites found in cruciferous vegetables (Brassicaceae) that are valued for their potential health benefits. Frequently consumed representatives of these vegetables, for example, are white or red cabbage, which are typically boiled before consumption. Recently, 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were identified as a class of thermal glucosinolate degradation products that are formed during the boiling of cabbage. Since these newly discovered compounds are frequently consumed, this raises questions about their potential uptake and their possible bioactive functions. Therefore, 3-allyl-4-hydroxythiazolidine-2-thione (allyl HTT) and 4-hydroxy-3-(4-(methylsulfinyl) butyl)thiazolidine-2-thione (4-MSOB HTT) as degradation products of the respective glucosinolates sinigrin and glucoraphanin were investigated. After consumption of boiled red cabbage broth, recoveries of consumed amounts of the degradation products in urine collected for 24 h were 18 +/- 5% for allyl HTT and 21 +/- 4% for 4-MSOB HTT (mean +/- SD, n = 3). To investigate the stability of the degradation products during uptake and to elucidate the uptake mechanism, both an in vitro stomach and an in vitro intestinal model were applied. The results indicate that the uptake of allyl HTT and 4-MSOB HTT occurs by passive diffusion. Both compounds show no acute cell toxicity, no antioxidant potential, and no change in NAD(P)H dehydrogenase quinone 1 (NQO1) activity up to 100 mu M. However, inhibition of glycogen synthase kinases-3 (GSK-3) in the range of 20% for allyl HTT for the isoform GSK-3 beta and 29% for 4-MSOB HTT for the isoform GSK-3 alpha at a concentration of 100 mu M was found. Neither health-promoting nor toxic effects of 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were found in the four tested assays carried out in this study, which contrasts with the properties of other glucosinolate degradation products, such as isothiocyanates. KW - stomach model KW - glycogen synthase kinase-3 KW - cytotoxicity KW - antioxidant potential KW - intestinal model KW - cellular uptake KW - isothiocyanate Y1 - 2022 U6 - https://doi.org/10.3389/fnut.2022.941286 SN - 2296-861X VL - 9 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Delpero, Manuel A1 - Arends, Danny A1 - Sprechert, Maximilian A1 - Krause, Florian A1 - Kluth, Oliver A1 - Schürmann, Annette A1 - Brockmann, Gudrun A. A1 - Hesse, Deike T1 - Identification of four novel QTL linked to the metabolic syndrome in the Berlin Fat Mouse JF - International journal of obesity / North American Association for the Study of Obesity N2 - Background The Berlin Fat Mouse Inbred line (BFMI) is a model for obesity and the metabolic syndrome. This study aimed to identify genetic variants associated with impaired glucose metabolism using the obese lines BFMI861-S1 and BFMI861-S2, which are genetically closely related, but differ in several traits. BFMI861-S1 is insulin resistant and stores ectopic fat in the liver, whereas BFMI861-S2 is insulin sensitive. Methods In generation 10, 397 males of an advanced intercross line (AIL) BFMI861-S1 x BFMI861-S2 were challenged with a high-fat, high-carbohydrate diet and phenotyped over 25 weeks. QTL-analysis was performed after selective genotyping of 200 mice using the GigaMUGA Genotyping Array. Additional 197 males were genotyped for 7 top SNPs in QTL regions. For the prioritization of positional candidate genes whole genome sequencing and gene expression data of the parental lines were used. Results Overlapping QTL for gonadal adipose tissue weight and blood glucose concentration were detected on chromosome (Chr) 3 (95.8-100.1 Mb), and for gonadal adipose tissue weight, liver weight, and blood glucose concentration on Chr 17 (9.5-26.1 Mb). Causal modeling suggested for Chr 3-QTL direct effects on adipose tissue weight, but indirect effects on blood glucose concentration. Direct effects on adipose tissue weight, liver weight, and blood glucose concentration were suggested for Chr 17-QTL. Prioritized positional candidate genes for the identified QTL were Notch2 and Fmo5 (Chr 3) and Plg and Acat2 (Chr 17). Two additional QTL were detected for gonadal adipose tissue weight on Chr 15 (67.9-74.6 Mb) and for body weight on Chr 16 (3.9-21.4 Mb). Conclusions QTL mapping together with a detailed prioritization approach allowed us to identify candidate genes associated with traits of the metabolic syndrome. In addition, we provided evidence for direct and indirect genetic effects on blood glucose concentration in the insulin-resistant mouse line BFMI861-S1. Y1 - 2022 U6 - https://doi.org/10.1038/s41366-021-00991-3 SN - 0307-0565 SN - 1476-5497 VL - 46 IS - 2 SP - 307 EP - 315 PB - Nature Publ. Group CY - Avenel, NJ ER - TY - JOUR A1 - Mühlenbruch, Kristin A1 - Zhuo, Xiaohui A1 - Bardenheier, Barbara A1 - Shao, Hui A1 - Laxy, Michael A1 - Icks, Andrea A1 - Zhang, Ping A1 - Gregg, Edward W. A1 - Schulze, Matthias Bernd T1 - Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention BT - a cost-effectiveness analysis JF - Acta Diabetologica N2 - Aims: Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA. Methods: We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001-2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group). Results: In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677-0.704) and 0.720 (0.707-0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs >= 5% were below $50,000/QALY gained. Conclusions: Intervening in those with >= 7% diabetes risk based on the GDRS or >= 9% on the ARIC 2009 score would be cost-effective. A risk score threshold >= 5% together with elevated FPG would also allow targeting interventions cost-effectively. KW - diabetes mellitus KW - type 2 KW - cost-effectiveness analysis KW - lifestyle risk reduction KW - clinical prediction rule Y1 - 2019 U6 - https://doi.org/10.1007/s00592-019-01451-1 SN - 0001-5563 SN - 0940-5429 SN - 1432-5233 VL - 57 IS - 4 SP - 447 EP - 454 PB - Springer CY - Mailand ER - TY - JOUR A1 - Döll, Stefanie A1 - Djalali Farahani-Kofoet, Roxana A1 - Zrenner, Rita A1 - Henze, Andrea A1 - Witzel, Katja T1 - Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates JF - Horticulture research N2 - Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as 'lipids and lipid-like molecules' or 'phenylpropanoids and polyketides'. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to 'lipid metabolism', 'biosynthesis of other secondary metabolites' and 'transport and catabolism', reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to 'transcription', 'translation' and 'folding, sorting and degradation', in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function. Y1 - 2021 U6 - https://doi.org/10.1038/s41438-021-00510-5 SN - 2052-7276 VL - 8 IS - 1 PB - Nanjing Agricultural Univ. CY - Nanjing ER - TY - JOUR A1 - Kuhn, Eugênia Carla A1 - Tavares Jacques, Maurício A1 - Teixeira, Daniela A1 - Meyer, Sören A1 - Gralha, Thiago A1 - Roehrs, Rafael A1 - Camargo, Sandro A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia A1 - Ávila, Daiana Silva T1 - Ecotoxicological assessment of Uruguay River and affluents pre- and biomonitoring JF - Environmental science and pollution research : ESPR N2 - Uruguay River is the most important river in western Rio Grande do Sul, separating Brazil from Argentina and Uruguay. However, its pollution is of great concern due to agricultural activities in the region and the extensive use of pesticides. In a long term, this practice leads to environmental pollution, especially to the aquatic system. The objective of this study was to analyze the physicochemical characteristics, metals and pesticides levels in water samples obtained before and after the planting and pesticides' application season from three sites: Uruguay River and two minor affluents, Mezomo Dam and Salso Stream. For biomonitoring, the free-living nematode Caenorhabditis elegans was used, which were exposed for 24 h. We did not find any significant alteration in physicochemical parameters. In the pre- and post-pesticides' samples we observed a residual presence of three pesticides (tebuconazole, imazethapyr, and clomazone) and metals which levels were above the recommended (As, Hg, Fe, and Mn). Exposure to both pre- and post-pesticides' samples impaired C. elegans reproduction and post-pesticides samples reduced worms' survival rate and lifespan. PCA analysis indicated that the presence of metals and pesticides are important variables that impacted C. elegans biological endpoints. Our data demonstrates that Uruguay River and two affluents are contaminated independent whether before or after pesticides' application season. In addition, it reinforces the usefulness of biological indicators, since simple physicochemical analyses are not sufficient to attest water quality and ecological safety. KW - Heavy metals KW - Pesticides KW - Contamination KW - Arsenic KW - Environmental KW - pollution KW - Uruguay River Y1 - 2021 U6 - https://doi.org/10.1007/s11356-020-11986-4 SN - 0944-1344 SN - 1614-7499 VL - 28 IS - 17 SP - 21730 EP - 21741 PB - Springer CY - Berlin ; Heidelberg ER - TY - JOUR A1 - Pan, Yuanwei A1 - Ma, Xuehua A1 - Liu, Chuang A1 - Xing, Jie A1 - Zhou, Suqiong A1 - Parshad, Badri A1 - Schwerdtle, Tanja A1 - Li, Wenzhong A1 - Wu, Aiguo A1 - Haag, Rainer T1 - Retinoic acid-loaded dendritic polyglycerol-conjugated gold nanostars for targeted photothermal therapy in breast cancer stem cells JF - ACS nano N2 - The existence of cancer stem cells (CSCs) poses a major obstacle for the success of current cancer therapies, especially the fact that non-CSCs can spontaneously turn into CSCs, which lead to the failure of the treatment and tumor relapse. Therefore, it is very important to develop effective strategies for the eradication of the CSCs. In this work, we have developed a CSCs-specific targeted, retinoic acid (RA)-loaded gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatform for the efficient eradication of CSCs. The nanocomposites possess good biocompatibility and exhibit effective CSCs-specific multivalent targeted capability due to hyaluronic acid (HA) decorated on the multiple attachment sites of the bioinert dendritic polyglycerol (dPG). With the help of CSCs differentiation induced by RA, the self-renewal of breast CSCs and tumor growth were suppressed by the high therapeutic efficacy of photothermal therapy (PTT) in a synergistic inhibitory manner. Moreover, the stemness gene expression and CSC-driven tumorsphere formation were significantly diminished. In addition, the in vivo tumor growth and CSCs were also effectively eliminated, which indicated superior anticancer activity, effective CSCs suppression, and prevention of relapse. Taken together, we developed a CSCs-specific targeted, RA-loaded GNSs-dPG nanoplatform for the targeted eradication of CSCs and for preventing the relapse. KW - cancer stem cells KW - dendritic polyglycerol KW - gold nanostars KW - retinoic acid KW - photothermal therapy Y1 - 2021 U6 - https://doi.org/10.1021/acsnano.1c05452 SN - 1936-0851 SN - 1936-086X VL - 15 IS - 9 SP - 15069 EP - 15084 PB - American Chemical Society CY - Washington ER - TY - THES A1 - Rinne, Theresa Charlotte T1 - The effects of nutrients on bone stem cell function and regeneration N2 - Aging is associated with bone loss, which can lead to osteoporosis and high fracture risk. This coincides with the enhanced formation of bone marrow adipose tissue (BMAT), suggesting a negative effect of bone marrow adipocytes on skeletal health. Increased BMAT formation is also observed in pathologies such as obesity, type 2 diabetes and osteoporosis. However, a subset of bone marrow adipocytes forming the constitutive BMAT (cBMAT), arise early in life in the distal skeleton, contain high levels of unsaturated fatty acids and are thought to provide a physiological function. Regulated BMAT (rBMAT) forms during aging and obesity in proximal regions of the bone and contain a large proportion of saturated fatty acids. Paradoxically, BMAT accumulation is also enhanced during caloric restriction (CR), a life-span extending dietary intervention. This indicates, that different types of BMAT can form in response to opposing nutritional stimuli with potentially different functions. To this end, two types of nutritional interventions, CR and high fat diet (HFD), that are both described to induce BMAT accumulation were carried out. CR markedly increased BMAT formation in the proximal tibia and led to a higher proportion of unsaturated fatty acids, making it similar to the physiological cBMAT. Additionally, proximal and diaphyseal tibia regions displayed higher adiponectin expression. In aged mice, CR was associated with an improved trabecular bone structure. Taken together, these findings demonstrate, that the type of BMAT that forms during CR might provide beneficial effects for local bone stem/progenitor cells and metabolic health. The HFD intervention performed in this thesis showed no effect on BMAT accumulation and bone microstructure. RNA Seq analysis revealed alterations in the composition of the collagen-containing extracellular matrix (ECM). In order to investigate the effects of glucose homeostasis on osteogenesis, differentiation capacity of immortalized multipotent mesenchymal stromal cells (MSCs) and osteochondrogenic progenitor cells (OPCs) was analyzed. Insulin improved differentiation in both cell types, however, combination of with a high glucose concentration led to an impaired mineralization of the ECM. In the MSCs, this was accompanied by the formation of adipocytes, indicating negative effects of the adipocytes formed during hyperglycemic conditions on mineralization processes. However, the altered mineralization pattern and structure of the ECM was also observed in OPCs, which did not form any adipocytes, suggesting further negative effects of a hyperglycemic environment on osteogenic differentiation. In summary, the work provided in this thesis demonstrated that differentiation commitment of bone-resident stem cells can be altered through nutrient availability, specifically glucose. Surprisingly, both high nutrient supply, e.g. the hyperglycemic cell culture conditions, and low nutrient supply, e.g. CR, can induce adipogenic differentiation. However, while CR-induced adipocyte formation was associated with improved trabecular bone structure, adipocyte formation in a hyperglycemic cell-culture environment hampered mineralization. This thesis provides further evidence for the existence of different types of BMAT with specific functions. Y1 - 2024 ER - TY - JOUR A1 - Sellem, Laury A1 - Antoni, Rona A1 - Koutsos, Athanasios A1 - Ozen, Ezgi A1 - Wong, Gloria A1 - Ayyad, Hasnaa A1 - Weech, Michelle A1 - Schulze, Matthias Bernd A1 - Wernitz, Andreas A1 - Fielding, Barbara A. A1 - Robertson, M. Denise A1 - Jackson, Kim G. A1 - Griffin, Bruce A. A1 - Lovegrove, Julie A. T1 - Impact of a food-based dietary fat exchange model for replacing dietary saturated with unsaturated fatty acids in healthy men on plasma phospholipids fatty acid profiles and dietary patterns JF - European journal of nutrition N2 - Purpose UK guidelines recommend dietary saturated fatty acids (SFAs) should not exceed 10% total energy (%TE) for cardiovascular disease prevention, with benefits observed when SFAs are replaced with unsaturated fatty acids (UFAs). This study aimed to assess the efficacy of a dietary exchange model using commercially available foods to replace SFAs with UFAs. Methods Healthy men (n = 109, age 48, SD 11 year) recruited to the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention-1 (RISSCI-1) study (ClinicalTrials.Gov n degrees NCT03270527) followed two sequential 4-week isoenergetic moderate-fat (34%TE) diets: high-SFA (18%TE SFAs, 16%TE UFAs) and low-SFA (10%TE SFAs, 24%TE UFAs). Dietary intakes were assessed using 4-day weighed diet diaries. Nutrient intakes were analysed using paired t-tests, fasting plasma phospholipid fatty acid (PL-FA) profiles and dietary patterns were analysed using orthogonal partial least square discriminant analyses. Results Participants exchanged 10.2%TE (SD 4.1) SFAs for 9.7%TE (SD 3.9) UFAs between the high and low-SFA diets, reaching target intakes with minimal effect on other nutrients or energy intakes. Analyses of dietary patterns confirmed successful incorporation of recommended foods from commercially available sources (e.g. dairy products, snacks, oils, and fats), without affecting participants' overall dietary intakes. Analyses of plasma PL-FAs indicated good compliance to the dietary intervention and foods of varying SFA content. Conclusions RISSCI-1 dietary exchange model successfully replaced dietary SFAs with UFAs in free-living healthy men using commercially available foods, and without altering their dietary patterns. Further intervention studies are required to confirm utility and feasibility of such food-based dietary fat replacement models at a population level. KW - Dietary fat composition KW - Food-exchange model KW - Dietary compliance KW - Dairy biomarkers KW - Dietary fat replacement Y1 - 2022 U6 - https://doi.org/10.1007/s00394-022-02910-2 SN - 1436-6207 SN - 1436-6215 VL - 61 IS - 7 SP - 3669 EP - 3684 PB - Springer CY - Heidelberg ER - TY - CHAP A1 - Michaelis, Vivien A1 - Aengenheister, Leonie A1 - Schwerdtle, Tanja A1 - Buerki-Thurnherr, Tina A1 - Bornhorst, Julia T1 - Manganese translocation across an in vitro model of human villous trophoblast T2 - Placenta Y1 - 2021 SN - 0143-4004 SN - 1532-3102 VL - 112 SP - E63 EP - E64 PB - Elsevier CY - Amsterdam [u.a.] ER - TY - JOUR A1 - Jannasch, Franziska A1 - Nickel, Daniela A1 - Schulze, Matthias Bernd T1 - The reliability and relative validity of predefined dietary patterns were higher than that of exploratory dietary patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam population JF - British journal of nutrition : BJN : an international journal of nutritional science / published on behalf of The Nutrition Society N2 - The aim of this study was to assess the ability of the FFQ to describe reliable and valid dietary pattern (DP) scores. In a total of 134 participants of the European Prospective Investigation into Cancer and Nutrition-Potsdam study aged 35-67 years, the FFQ was applied twice (baseline and after 1 year) to assess its reliability. Between November 1995 and March 1997, twelve 24-h dietary recalls (24HDR) as reference instrument were applied to assess the validity of the FFQ. Exploratory DP were derived by principal component analyses. Investigated predefined DP were the Alternative Healthy Eating Index (AHEI) and two Mediterranean diet indices. From dietary data of each FFQ, two exploratory DP were retained, but differed in highly loading food groups, resulting in moderate correlations (r 0 center dot 45-0 center dot 58). The predefined indices showed higher correlations between the FFQ (r(AHEI) 0 center dot 62, r(Mediterranean Diet Pyramid Index (MedPyr)) 0 center dot 62 and r(traditional Mediterranean Diet Score (tMDS)) 0 center dot 51). From 24HDR dietary data, one exploratory DP retained differed in composition to the first FFQ-based DP, but showed similarities to the second DP, reflected by a good correlation (r 0 center dot 70). The predefined DP correlated moderately (r 0 center dot 40-0 center dot 60). To conclude, long-term analyses on exploratory DP should be interpreted with caution, due to only moderate reliability. The validity differed extensively for the two exploratory DP. The investigated predefined DP showed a better reliability and a moderate validity, comparable to other studies. Within the two Mediterranean diet indices, the MedPyr performed better than the tMDs in this middle-aged, semi-urban German study population. KW - dietary patterns KW - reliability KW - validity Y1 - 2020 U6 - https://doi.org/10.1017/S0007114520003517 SN - 1475-2662 SN - 0007-1145 VL - 125 IS - 11 SP - 1270 EP - 1280 PB - Cambridge University Press CY - Cambridge ER - TY - JOUR A1 - Varão Moura, Alexandre A1 - Aparecido Rosini Silva, Alex A1 - Domingos Santo da Silva, José A1 - Aleixo Leal Pedroza, Lucas A1 - Bornhorst, Julia A1 - Stiboller, Michael A1 - Schwerdtle, Tanja A1 - Gubert, Priscila T1 - Determination of ions in Caenorhabditis elegans by ion chromatography JF - Journal of chromatography. B N2 - The Caenorhabditis elegans (C. elegans) is a model organism that has been increasingly used in health and environmental toxicity assessments. The quantification of such elements in vivo can assist in studies that seek to relate the exposure concentration to possible biological effects. Therefore, this study is the first to propose a method of quantitative analysis of 21 ions by ion chromatography (IC), which can be applied in different toxicity studies in C. elegans. The developed method was validated for 12 anionic species (fluoride, acetate, chloride, nitrite, bromide, nitrate, sulfate, oxalate, molybdate, dichromate, phosphate, and perchlorate), and 9 cationic species (lithium, sodium, ammonium, thallium, potassium, magnesium, manganese, calcium, and barium). The method did not present the presence of interfering species, with R2 varying between 0.9991 and 0.9999, with a linear range from 1 to 100 mu g L-1. Limits of detection (LOD) and limits of quantification (LOQ) values ranged from 0.2319 mu g L-1 to 1.7160 mu g L-1 and 0.7028 mu g L-1 to 5.1999 mu g L-1, respectively. The intraday and interday precision tests showed an Relative Standard Deviation (RSD) below 10.0 % and recovery ranging from 71.0 % to 118.0 % with a maximum RSD of 5.5 %. The method was applied to real samples of C. elegans treated with 200 uM of thallium acetate solution, determining the uptake and bioaccumulated Tl+ content during acute exposure. KW - ion chromatography KW - C. elegans KW - method development KW - method validation KW - ion quantification Y1 - 2022 U6 - https://doi.org/10.1016/j.jchromb.2022.123312 SN - 1570-0232 SN - 1873-376X VL - 1204 PB - Elsevier CY - Amsterdam [u.a.] ER - TY - JOUR A1 - Schmiedeskamp, Amy A1 - Schreiner, Monika A1 - Baldermann, Susanne T1 - Impact of cultivar selection and thermal processing by air drying, air frying, and deep frying on the carotenoid content and stability and antioxidant capacity in carrots (Daucus carota L.) JF - Journal of agricultural and food chemistry : a publication of the American Chemical Society N2 - Epidemiological data suggest that consuming diets rich in carotenoids can reduce the risk of developing several non-communicable diseases. Thus, we investigated the extent to which carotenoid contents of foods can be increased by the choice of food matrices with naturally high carotenoid contents and thermal processing methods that maintain their stability. For this purpose, carotenoids of 15 carrot (Daucus carota L.) cultivars of different colors were assessed with UHPLC-DAD-ToF-MS. Additionally, the processing effects of air drying, air frying, and deep frying on carotenoid stability were applied. Cultivar selection accounted for up to 12.9-fold differences in total carotenoid content in differently colored carrots and a 2.2-fold difference between orange carrot cultivars. Air frying for 18 and 25 min and deep frying for 10 min led to a significant decrease in total carotenoid contents. TEAC assay of lipophilic extracts showed a correlation between carotenoid content and antioxidant capacity in untreated carrots. KW - air-dried KW - air-fried KW - deep-fried KW - domestic cooking KW - TEAC KW - color KW - Daucus KW - carota L Y1 - 2022 U6 - https://doi.org/10.1021/acs.jafc.1c05718 SN - 0021-8561 SN - 1520-5118 VL - 70 IS - 5 SP - 1629 EP - 1639 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Jonas, Wenke A1 - Kluth, Oliver A1 - Helms, Anett A1 - Voss, Sarah A1 - Jahnert, Markus A1 - Gottmann, Pascal A1 - Speckmann, Thilo A1 - Knebel, Birgit A1 - Chadt, Alexandra A1 - Al-Hasani, Hadi A1 - Schürmann, Annette A1 - Vogel, Heike T1 - Identification of novel genes involved in hyperglycemia in mice JF - International journal of molecular sciences N2 - Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function. KW - beta-cell KW - diabetes KW - proliferation KW - apoptosis KW - QTL Y1 - 2022 U6 - https://doi.org/10.3390/ijms23063205 SN - 1661-6596 SN - 1422-0067 VL - 23 IS - 6 PB - MDPI CY - Basel ER - TY - THES A1 - Fitzner, Maria T1 - Cultivation of selected halophytes in saline indoor farming and modulation of cultivation conditions to optimize metabolite profiles for human nutrition T1 - Kultivierung ausgewählter Halophyten im salinen Indoor Farming und Modulation der Anbaubedingungen zur Optimierung der Metabolitenprofile für die menschliche Ernährung N2 - With the many challenges facing the agricultural system, such as water scarcity, loss of arable land due to climate change, population growth, urbanization or trade disruptions, new agri-food systems are needed to ensure food security in the future. In addition, healthy diets are needed to combat non-communicable diseases. Therefore, plant-based diets rich in health-promoting plant secondary metabolites are desirable. A saline indoor farming system is representing a sustainable and resilient new agrifood system and can preserve valuable fresh water. Since indoor farming relies on artificial lighting, assessment of lighting conditions is essential. In this thesis, the cultivation of halophytes in a saline indoor farming system was evaluated and the influence of cultivation conditions were assessed in favor of improving the nutritional quality of halophytes for human consumption. Therefore, five selected edible halophyte species (Brassica oleracea var. palmifolia, Cochlearia officinalis, Atriplex hortensis, Chenopodium quinoa, and Salicornia europaea) were cultivated in saline indoor farming. The halophyte species were selected for to their salt tolerance levels and mechanisms. First, the suitability of halophytes for saline indoor farming and the influence of salinity on their nutritional properties, e.g. plant secondary metabolites and minerals, were investigated. Changes in plant performance and nutritional properties were observed as a function of salinity. The response to salinity was found to be species-specific and related to the salt tolerance mechanism of the halophytes. At their optimal salinity levels, the halophytes showed improved carotenoid content. In addition, a negative correlation was found between the nitrate and chloride content of halophytes as a function of salinity. Since chloride and nitrate can be antinutrient compounds, depending on their content, monitoring is essential, especially in halophytes. Second, regional brine water was introduced as an alternative saline water resource in the saline indoor farming system. Brine water was shown to be feasible for saline indoor farming of halophytes, as there was no adverse effect on growth or nutritional properties, e.g. carotenoids. Carotenoids were shown to be less affected by salt composition than by salt concentration. In addition, the interaction between the salinity and the light regime in indoor farming and greenhouse cultivation has been studied. There it was shown that interacting light regime and salinity alters the content of carotenoids and chlorophylls. Further, glucosinolate and nitrate content were also shown to be influenced by light regime. Finally, the influence of UVB light on halophytes was investigated using supplemental narrow-band UVB LEDs. It was shown that UVB light affects the growth, phenotype and metabolite profile of halophytes and that the UVB response is species specific. Furthermore, a modulation of carotenoid content in S. europaea could be achieved to enhance health-promoting properties and thus improve nutritional quality. This was shown to be dose-dependent and the underlying mechanisms of carotenoid accumulation were also investigated. Here it was revealed that carotenoid accumulation is related to oxidative stress. In conclusion, this work demonstrated the potential of halophytes as alternative vegetables produced in a saline indoor farming system for future diets that could contribute to ensuring food security in the future. To improve the sustainability of the saline indoor farming system, LED lamps and regional brine water could be integrated into the system. Since the nutritional properties have been shown to be influenced by salt, light regime and UVB light, these abiotic stressors must be taken into account when considering halophytes as alternative vegetables for human nutrition. N2 - Angesichts zahlreicher Herausforderungen wie Wasserknappheit oder Verlust landwirtschaftlicher Nutzflächen aufgrund des Klimawandels, Bevölkerungswachstum und Verstädterung sind neue Systeme der Agrar- und Lebensmittelproduktion (Agrifood-Systeme) erforderlich, um die Ernährungssicherheit in der Zukunft zu gewährleisten. Eines dieser neuen Agrifood-Systeme ist das Indoor Farming. Es bietet den Vorteil einer nachhaltigen und resilienten Nahrungsmittelproduktion. In Kombination mit dem Anbau von Salzpflanzen kann wertvolles Süßwasser eingespart werden, da diese mit Salzwasser bewässert werden können. Durch eine pflanzliche Ernährung, die reich an sekundären Pflanzenstoffen mit gesundheitsfördernden Eigenschaften ist, kann eine gesunde Ernährung erreicht werden. Dadurch kann das Risiko für nicht übertragbare Krankheiten wie Diabetes oder Herz-Kreislauf-Erkrankungen gesenkt werden. In dieser Arbeit wurde untersucht, ob salztolerante Pflanzen (Halophyten) als alternatives Gemüse für die menschliche Ernährung geeignet sind und ob sie in einem salzhaltigen Indoor Farming System angebaut werden können. Zu diesem Zweck wurden fünf essbare Halophyten (Palmkohl, Gartenmelde, Löffelkraut, Quinoa und Europäische Queller) untersucht. Mit diesen Halophyten wurden verschiedene Pflanzenstudien durchgeführt, um den Einfluss von Salz, Licht und UVB-Strahlung auf für die menschliche Ernährung relevante Inhaltsstoffe zu untersuchen. In der ersten Studie wurde untersucht, welchen Einfluss das salzhaltige Indoor Farming System auf die Salzpflanzen und ihre Inhaltsstoffe hat. Es konnte festgestellt werden, dass sich die Inhaltsstoffe mit steigender Salzkonzentration im Wasser verändern. Weiterhin wurde untersucht, ob sich regionales Solewasser aus einer Thermalquelle als Salzwasserressource eignet. Es zeigte sich, dass das Solewasser keine negativen Auswirkungen auf das Wachstum oder die Inhaltsstoffe hat. Darüber hinaus wurde das Indoor-Farming System mit dem klassischen Gewächshausanbau von Salzpflanzen verglichen. Dabei zeigte sich ein Einfluss der unterschiedlichen Beleuchtung auf die Inhaltsstoffe. Schließlich wurde der Einsatz von UVB-LEDs als zusätzliche Beleuchtung getestet. Dabei wurde eine Verbesserung des Inhaltsstoffprofils erreicht. Zusammenfassend konnte in dieser Arbeit gezeigt werden, dass Salzpflanzen in Indoor-Farming kultiviert werden können und dass die ernährungsphysiologischen Eigenschaften durch Salz, Beleuchtung und UVB-Licht beeinflusst werden können. KW - halophytes KW - indoor farming KW - secondary plant metabolites KW - carotenoids KW - saline agriculture KW - future food KW - human diet KW - Carotinoide KW - Nahrung der Zukunft KW - Halophyten KW - menschliche Ernährung KW - Indoor farming KW - Saline Landwirtschaft KW - pflanzliche Sekundär Metabolite Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-626974 ER - TY - JOUR A1 - Fitzner, Maria A1 - Fricke, Anna A1 - Schreiner, Monika A1 - Baldermann, Susanne T1 - Utilization of regional natural brines for the indoor cultivation of Salicornia europaea JF - Sustainability / Multidisciplinary Digital Publishing Institute (MDPI) N2 - Scaling agriculture to the globally rising population demands new approaches for future crop production such as multilayer and multitrophic indoor farming. Moreover, there is a current trend towards sustainable local solutions for aquaculture and saline agriculture. In this context, halophytes are becoming increasingly important for research and the food industry. As Salicornia europaea is a highly salt-tolerant obligate halophyte that can be used as a food crop, indoor cultivation with saline water is of particular interest. Therefore, finding a sustainable alternative to the use of seawater in non-coastal regions is crucial. Our goal was to determine whether natural brines, which are widely distributed and often available in inland areas, provide an alternative water source for the cultivation of saline organisms. This case study investigated the potential use of natural brines for the production of S. europaea. In the control group, which reflects the optimal growth conditions, fresh weight was increased, but there was no significant difference between the treatment groups comparing natural brines with artificial sea water. A similar pattern was observed for carotenoids and chlorophylls. Individual components showed significant differences. However, within treatments, there were mostly no changes. In summary, we showed that the influence of the different chloride concentrations was higher than the salt composition. Moreover, nutrient-enriched natural brine was demonstrated to be a suitable alternative for cultivation of S. europaea in terms of yield and nutritional quality. Thus, the present study provides the first evidence for the future potential of natural brine waters for the further development of aquaculture systems and saline agriculture in inland regions. KW - carotenoids KW - glasswort KW - land-based aquaculture KW - seawater KW - phytochemicals KW - halophytes KW - salt composition KW - chlorophylls KW - artificial KW - salt KW - saline agriculture Y1 - 2021 U6 - https://doi.org/10.3390/su132112105 SN - 2071-1050 VL - 13 IS - 21 PB - MDPI CY - Basel ER - TY - JOUR A1 - Wigger, Dominik A1 - Schumacher, Fabian A1 - Schneider-Schaulies, Sibylle A1 - Kleuser, Burkhard T1 - Sphingosine 1-phosphate metabolism and insulin signaling JF - Cellular signalling N2 - Insulin is the main anabolic hormone secreted by 13-cells of the pancreas stimulating the assimilation and storage of glucose in muscle and fat cells. It modulates the postprandial balance of carbohydrates, lipids and proteins via enhancing lipogenesis, glycogen and protein synthesis and suppressing glucose generation and its release from the liver. Resistance to insulin is a severe metabolic disorder related to a diminished response of peripheral tissues to the insulin action and signaling. This leads to a disturbed glucose homeostasis that precedes the onset of type 2 diabetes (T2D), a disease reaching epidemic proportions. A large number of studies reported an association between elevated circulating fatty acids and the development of insulin resistance. The increased fatty acid lipid flux results in the accumulation of lipid droplets in a variety of tissues. However, lipid intermediates such as diacylglycerols and ceramides are also formed in response to elevated fatty acid levels. These bioactive lipids have been associated with the pathogenesis of insulin resistance. More recently, sphingosine 1-phosphate (S1P), another bioactive sphingolipid derivative, has also been shown to increase in T2D and obesity. Although many studies propose a protective role of S1P metabolism on insulin signaling in peripheral tissues, other studies suggest a causal role of S1P on insulin resistance. In this review, we critically summarize the current state of knowledge of S1P metabolism and its modulating role on insulin resistance. A particular emphasis is placed on S1P and insulin signaling in hepatocytes, skeletal muscle cells, adipocytes and pancreatic 13-cells. In particular, modulation of receptors and enzymes that regulate S1P metabolism can be considered as a new therapeutic option for the treatment of insulin resistance and T2D. KW - Insulin resistance KW - Type 2 diabetes KW - Sphingolipids KW - Hepatocytes KW - Adipocytes KW - Skeletal muscle cells Y1 - 2021 U6 - https://doi.org/10.1016/j.cellsig.2021.109959 SN - 0898-6568 SN - 1873-3913 VL - 82 PB - Elsevier Science CY - Amsterdam [u.a.] ER - TY - THES A1 - Henning, Thorsten T1 - Cross-sectional associations of dietary biomarker patterns with health and nutritional status Y1 - 2024 ER - TY - THES A1 - Harbart, Vanessa T1 - The effect of protected cultivation on the nutritional quality of lettuce (Lactuca sativa var capitata L.) with a focus on antifogging additives in polyolefin covers T1 - Die Bedeutung des geschützten Anbaus für die ernährungsphysiologische Qualität von Kopfsalat (Lactuca sativa var. capitata L.) mit Schwerpunkt auf Antibeschlagmittel in Polyolefinfolien N2 - Protected cultivation in greenhouses or polytunnels offers the potential for sustainable production of high-yield, high-quality vegetables. This is related to the ability to produce more on less land and to use resources responsibly and efficiently. Crop yield has long been considered the most important factor. However, as plant-based diets have been proposed for a sustainable food system, the targeted enrichment of health-promoting plant secondary metabolites should be addressed. These metabolites include carotenoids and flavonoids, which are associated with several health benefits, such as cardiovascular health and cancer protection. Cover materials generally have an influence on the climatic conditions, which in turn can affect the levels of secondary metabolites in vegetables grown underneath. Plastic materials are cost-effective and their properties can be modified by incorporating additives, making them the first choice. However, these additives can migrate and leach from the material, resulting in reduced service life, increased waste and possible environmental release. Antifogging additives are used in agricultural films to prevent the formation of droplets on the film surface, thereby increasing light transmission and preventing microbiological contamination. This thesis focuses on LDPE/EVA covers and incorporated antifogging additives for sustainable protected cultivation, following two different approaches. The first addressed the direct effects of leached antifogging additives using simulation studies on lettuce leaves (Lactuca sativa var capitata L). The second determined the effect of antifog polytunnel covers on lettuce quality. Lettuce is usually grown under protective cover and can provide high nutritional value due to its carotenoid and flavonoid content, depending on the cultivar. To study the influence of simulated leached antifogging additives on lettuce leaves, a GC-MS method was first developed to analyze these additives based on their fatty acid moieties. Three structurally different antifogging additives (reference material) were characterized outside of a polymer matrix for the first time. All of them contained more than the main fatty acid specified by the manufacturer. Furthermore, they were found to adhere to the leaf surface and could not be removed by water or partially by hexane. The incorporation of these additives into polytunnel covers affects carotenoid levels in lettuce, but not flavonoids, caffeic acid derivatives and chlorophylls. Specifically, carotenoids were higher in lettuce grown under polytunnels without antifog than with antifog. This has been linked to their effect on the light regime and was suggested to be related to carotenoid function in photosynthesis. In terms of protected cultivation, the use of LDPE/EVA polytunnels affected light and temperature, and both are closely related. The carotenoid and flavonoid contents of lettuce grown under polytunnels was reversed, with higher carotenoid and lower flavonoid levels. At the individual level, the flavonoids detected in lettuce did not differ however, lettuce carotenoids adapted specifically depending on the time of cultivation. Flavonoid reduction was shown to be transcriptionally regulated (CHS) in response to UV light (UVR8). In contrast, carotenoids are thought to be regulated post-transcriptionally, as indicated by the lack of correlation between carotenoid levels and transcripts of the first enzyme in carotenoid biosynthesis (PSY) and a carotenoid degrading enzyme (CCD4), as well as the increased carotenoid metabolic flux. Understanding the regulatory mechanisms and metabolite adaptation strategies could further advance the strategic development and selection of cover materials. N2 - Der geschützte Anbau in Gewächshäusern oder unter Folientunneln bietet die Möglichkeit einer nachhaltigen Produktion von ertragreichem Gemüse hoher Qualität. Die ressourceneffiziente Produktion von mehr auf weniger Fläche ist dabei ein wichtiger Faktor. Lange galt der Gemüseertrag als wichtigstes Kriterium. Die Anreicherung von gesundheitsfördernden sekundären Pflanzenmetaboliten gewinnt jedoch zunehmend an Bedeutung, nicht zuletzt durch die empfohlene pflanzenbasierte Ernährung für ein nachhaltiges Ernährungssystem. Die Sekundärmetabolite Carotinoide und Flavonoide sind mit verschiedenen gesundheitlichen Vorteilen assoziiert, etwa der kardiovaskulären Gesundheit und der Krebsprävention. Das Material eines Gewächshauses beeinflusst die klimatischen Bedingungen im geschützten Anbau. Das resultierende Mikroklima kann sich wiederum auf den Gehalt an Sekundärmetaboliten im Gemüse auswirken. Materialien aus Kunststoff sind kostengünstig und ihre Eigenschaften können durch Zusätze, sogenannte Additive, modifiziert werden. Additive können an die Oberfläche des Materials und aus diesem migrieren, was die Materiallebensdauer einerseits verkürzt und größere Abfallmengen produziert. Andererseits besteht das Risiko einer Umweltemission der Additive. Antifogging-Additive verhindern die Bildung von Kondenswasser Tropfen auf der Oberfläche von Gewächshausfolien, wodurch die Lichtdurchlässigkeit der Folien verbessert, sowie eine mikrobiologische Kontamination vermieden werden kann. Die vorliegende Arbeit befasst sich mit LDPE/EVA-Gewächshausfolien mit Antifogging-Additiven für einen nachhaltigen geschützten Anbau und verfolgt dabei zwei unterschiedliche Herangehensweisen. Zum einen befasst sich die Arbeit mit den direkten Auswirkungen von Antifogging-Additiven in Folge eines Übergangs auf Salatblätter (Lactuca sativa var. capitata L.) mittels Simulationsversuchen. Um den simulierten Übergang zu untersuchen, wurde zunächst eine Methode zur Analyse des Fettsäureanteils der Additive mittels GC-MS entwickelt. Drei strukturell unterschiedliche Antifogging-Additive (Referenzmaterial) wurden erstmals außerhalb einer Polymermatrix charakterisiert. Sie enthielten diverse Fettsäuren, und somit mehr, als die vom Hersteller angegebene Hauptfettsäure. Des Weiteren wurde gezeigt, dass sie an der Blattoberfläche haften und weder durch Wasser noch teilweise durch Hexan entfernt werden können. Zum anderen wurde der Einfluss von Antifogging-Additiven in Gewächshausfolien auf die Salatqualität untersucht. Salat ist ein Gemüse, das üblicherweise auch unter Schutzabdeckungen angebaut wird und sortenspezifisch größere Mengen an Carotinoiden und Flavonoiden enthält. Der Anbau von Salat unter Antifog-Folientunneln beeinflusste den Carotinoidgehalt, nicht aber den Gehalt an Flavonoiden, Kaffeesäurederivaten und Chlorophyll. Salate, die unter Folientunneln ohne Antifog angebaut wurde akkumulierten höhere Gehalte der Carotinoide, als solche unter Antifog-Folientunneln. Es besteht wahrscheinlich ein Zusammenhang mit der Funktion der Carotinoide als Photosynthesepigmente und der Lichtumgebung. Die Verwendung von LDPE/EVA-Folientunneln beeinflusste allgemein Licht und Temperatur im geschützten Anbau, beide Faktoren sind eng verknüpft. Die Carotinoid- und Flavonoidgehalte waren dabei invers, mit höheren gesamt Carotinoid- und niedrigeren gesamt Flavonoidgehalten von Salaten unter Folientunneln. Die individuellen Flavonoid-Glykoside unterschieden sich innerhalb der Versuchszeiträume (Frühjahr und Herbst) nicht. Es konnte gezeigt werden, dass diese hinsichtlich der UV-Lichtumgebung (UVR8) transkriptionell reguliert werden (CHS). Demgegenüber fanden spezifische Anpassungen der individuellen Carotinoidmetabolite in den Versuchszeiträumen statt. Die fehlende Korrelation der Carotinoidmetabolite und der Transkripte des Hauptenzyms der Biosynthese (PSY) und eines Carotinoid-abbauenden Enzyms (CCD4) sowie der erhöhte Carotinoid-Stoffwechselfluss deuten auf eine post-transkriptionelle Regulierung hin. Die Regulationsmechanismen und Anpassungsstrategien der sekundären Pflanzenstoffe in Gemüse zu verstehen, könnte zukünftig zur strategischen Entwicklung und Auswahl von Gewächshausmaterialien beitragen. KW - protected cultivation KW - polytunnel KW - lettuce KW - antifogging additives KW - plant secondary metabolites KW - carotenoids KW - flavonoids KW - mass spectrometry KW - plastic additives KW - Antibeschlag-Additive KW - Carotinoide KW - Flavonoide KW - Kopfsalat KW - Massenspektrometrie KW - sekundäre Pflanzenstoffe KW - Kunststoff-Additive KW - Folientunnel KW - geschützter Anbau Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-629375 ER - TY - GEN A1 - Baesler, Jessica A1 - Michaelis, Vivien A1 - Stiboller, Michael A1 - Haase, Hajo A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Sturzenbaum, Stephen R. A1 - Bornhorst, Julia T1 - Nutritive manganese and zinc overdosing in aging c. elegans result in a metallothionein-mediated alteration in metal homeostasis T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1364 KW - aging KW - C. elegans KW - homeostasis KW - manganese KW - zinc Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-514995 SN - 1866-8372 IS - 8 ER - TY - GEN A1 - Perez-Cornago, Aurora A1 - Crowe, Francesca L. A1 - Appleby, Paul N. A1 - Bradbury, Kathryn E. A1 - Wood, Angela M. A1 - Jakobsen, Marianne Uhre A1 - Johnson, Laura A1 - Sacerdote, Carlotta A1 - Steur, Marinka A1 - Weiderpass, Elisabete A1 - Wurtz, Anne Mette L. A1 - Kuhn, Tilman A1 - Katzke, Verena A1 - Trichopoulou, Antonia A1 - Karakatsani, Anna A1 - La Vecchia, Carlo A1 - Masala, Giovanna A1 - Tumino, Rosario A1 - Panico, Salvatore A1 - Sluijs, Ivonne A1 - Skeie, Guri A1 - Imaz, Liher A1 - Petrova, Dafina A1 - Quiros, J. Ramon A1 - Yohar, Sandra Milena Colorado A1 - Jakszyn, Paula A1 - Melander, Olle A1 - Sonestedt, Emily A1 - Andersson, Jonas A1 - Wennberg, Maria A1 - Aune, Dagfinn A1 - Riboli, Elio A1 - Schulze, Matthias Bernd A1 - di Angelantonio, Emanuele A1 - Wareham, Nicholas J. A1 - Danesh, John A1 - Forouhi, Nita G. A1 - Butterworth, Adam S. A1 - Key, Timothy J. T1 - Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Background: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD. Results: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, Ptrend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk. Conclusions: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1367 KW - fruit KW - vegetables KW - legumes KW - nuts KW - seeds KW - coronary heart disease Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-560340 SN - 1866-8372 IS - 1 ER - TY - GEN A1 - Christakoudi, Sofia A1 - Pagoni, Panagiota A1 - Ferrari, Pietro A1 - Cross, Amanda J. A1 - Tzoulaki, Ioanna A1 - Muller, David C. A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Murphy, Neil A1 - Dossus, Laure A1 - Turzanski Fortner, Renee A1 - Agudo, Antonio A1 - Overvad, Kim A1 - Perez-Cornago, Aurora A1 - Key, Timothy J. A1 - Brennan, Paul A1 - Johansson, Mattias A1 - Tjonneland, Anne A1 - Halkjaer, Jytte A1 - Boutron-Ruault, Marie-Christine A1 - Artaud, Fanny A1 - Severi, Gianluca A1 - Kaaks, Rudolf A1 - Schulze, Matthias Bernd A1 - Bergmann, Manuela M. A1 - Masala, Giovanna A1 - Grioni, Sara A1 - Simeon, Vittorio A1 - Tumino, Rosario A1 - Sacerdote, Carlotta A1 - Skeie, Guri A1 - Rylander, Charlotta A1 - Borch, Kristin Benjaminsen A1 - Quiros, J. Ramon A1 - Rodriguez-Barranco, Miguel A1 - Chirlaque, Maria-Dolores A1 - Ardanaz, Eva A1 - Amiano, Pilar A1 - Drake, Isabel A1 - Stocks, Tanja A1 - Haggstrom, Christel A1 - Harlid, Sophia A1 - Ellingjord-Dale, Merete A1 - Riboli, Elio A1 - Tsilidis, Konstantinos K. T1 - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1373 KW - BMI change KW - cancer KW - middle adulthood KW - weight gain KW - weight loss Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-573609 SN - 1866-8372 IS - 7 ER - TY - GEN A1 - Saberi Hosnijeh, Fatemeh A1 - Casabonne, Delphine A1 - Nieters, Alexandra A1 - Solans, Marta A1 - Naudin, Sabine A1 - Ferrari, Pietro A1 - Mckay, James D. A1 - Benavente, Yolanda A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Severi, Gianluca A1 - Boutron Ruault, Marie-Christine A1 - Besson, Caroline A1 - Agnoli, Claudia A1 - Masala, Giovanna A1 - Sacerdote, Carlotta A1 - Tumino, Rosario A1 - Huerta, Jose Maria A1 - Amiano, Pilar A1 - Rodriguez-Barranco, Miguel A1 - Bonet, Catalina A1 - Barricarte, Aurelio A1 - Christakoudi, Sofia A1 - Knuppel, Anika A1 - Bueno-de-Mesquita, Bas A1 - Schulze, Matthias Bernd A1 - Kaaks, Rudolf A1 - Canzian, Federico A1 - Spath, Florentin A1 - Jerkeman, Mats A1 - Rylander, Charlotta A1 - Tjonneland, Anne A1 - Olsen, Anja A1 - Borch, Kristin Benjaminsen A1 - Vermeulen, Roel T1 - Association between anthropometry and lifestyle factors and risk of B-cell lymphoma BT - an exposome-wide analysis T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1374 KW - exposome KW - exposome‐ wide association study KW - lifestyle KW - lymphoma KW - prospective study Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-573562 SN - 1866-8372 IS - 9 ER - TY - GEN A1 - Dwi Putra, Sulistyo Emantoko A1 - Reichetzeder, Christoph A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Slowinski, Torsten A1 - Chu, Chang A1 - Krämer, Bernhard K. A1 - Kleuser, Burkhard A1 - Hocher, Berthold T1 - Being born large for gestational age is associated with increased global placental DNA methylation T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001). T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1405 KW - fetal origins hypothesis KW - birth weight KW - repetitive elements KW - glucocorticoid receptor KW - nutrient transport KW - growth restriction KW - later health KW - pregnancy KW - genes KW - patterns Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-516289 SN - 1866-8372 IS - 1 ER - TY - JOUR A1 - Dwi Putra, Sulistyo Emantoko A1 - Reichetzeder, Christoph A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Slowinski, Torsten A1 - Chu, Chang A1 - Krämer, Bernhard K. A1 - Kleuser, Burkhard A1 - Hocher, Berthold T1 - Being born large for gestational age is associated with increased global placental DNA methylation JF - Scientific Reports N2 - Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001). KW - fetal origins hypothesis KW - birth weight KW - repetitive elements KW - glucocorticoid receptor KW - nutrient transport KW - growth restriction KW - later health KW - pregnancy KW - genes KW - patterns Y1 - 2020 U6 - https://doi.org/10.1038/s41598-020-57725-0 SN - 2045-2322 VL - 10 IS - 1 SP - 1 EP - 10 PB - Springer Nature CY - London ER - TY - GEN A1 - Lang, Judith A1 - Bohn, Patrick A1 - Bhat, Hilal A1 - Jastrow, Holger A1 - Walkenfort, Bernd A1 - Cansiz, Feyza A1 - Fink, Julian A1 - Bauer, Michael A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Lang, Karl S. T1 - Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1400 KW - immunology KW - infection KW - membrane fusion KW - phagocytosis KW - sphingolipids Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515661 SN - 1866-8372 IS - 1 ER - TY - JOUR A1 - Lang, Judith A1 - Bohn, Patrick A1 - Bhat, Hilal A1 - Jastrow, Holger A1 - Walkenfort, Bernd A1 - Cansiz, Feyza A1 - Fink, Julian A1 - Bauer, Michael A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Lang, Karl S. T1 - Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease JF - Nature Communications N2 - Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1(-/-) mice results in replication of HSV-1 and Asah1(-/-) mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol. KW - immunology KW - infection KW - membrane fusion KW - phagocytosis KW - sphingolipids Y1 - 2020 U6 - https://doi.org/10.1038/s41467-020-15072-8 SN - 2041-1723 VL - 11 IS - 1 SP - 1 EP - 15 PB - Nature Publishing Group UK CY - London ER - TY - GEN A1 - Harms, Laura M. A1 - Scalbert, Augustin A1 - Zamora-Ros, Raul A1 - Rinaldi, Sabina A1 - Jenab, Mazda A1 - Murphy, Neil A1 - Achaintre, David A1 - Tjønneland, Anne A1 - Olsen, Anja A1 - Overvad, Kim A1 - Aleksandrova, Krasimira T1 - Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations BT - a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0 center dot 66, 95 % CI 0 center dot 46, 0 center dot 96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0 center dot 58, 95 % CI 0 center dot 39, 0 center dot 86), 3,4-dihydroxyphenylpropionic acid (OR 0 center dot 63, 95 % CI 0 center dot 46, 0 center dot 87), ferulic acid (OR 0 center dot 65, 95 % CI 0 center dot 44, 0 center dot 96) and caffeic acid (OR 0 center dot 69, 95 % CI 0 center dot 51, 0 center dot 93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0 center dot 67, 95 % CI 0 center dot 48, 0 center dot 93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1404 KW - polyphenols KW - plasma measurements KW - C-reactive protein KW - inflammation KW - chronic diseases Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515774 SN - 1866-8372 IS - 2 ER - TY - JOUR A1 - Harms, Laura M. A1 - Scalbert, Augustin A1 - Zamora-Ros, Raul A1 - Rinaldi, Sabina A1 - Jenab, Mazda A1 - Murphy, Neil A1 - Achaintre, David A1 - Tjønneland, Anne A1 - Olsen, Anja A1 - Overvad, Kim A1 - Aleksandrova, Krasimira T1 - Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations BT - a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort JF - British Journal of Nutrition N2 - Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0 center dot 66, 95 % CI 0 center dot 46, 0 center dot 96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0 center dot 58, 95 % CI 0 center dot 39, 0 center dot 86), 3,4-dihydroxyphenylpropionic acid (OR 0 center dot 63, 95 % CI 0 center dot 46, 0 center dot 87), ferulic acid (OR 0 center dot 65, 95 % CI 0 center dot 44, 0 center dot 96) and caffeic acid (OR 0 center dot 69, 95 % CI 0 center dot 51, 0 center dot 93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0 center dot 67, 95 % CI 0 center dot 48, 0 center dot 93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies. KW - polyphenols KW - plasma measurements KW - C-reactive protein KW - inflammation KW - chronic diseases Y1 - 2019 U6 - https://doi.org/10.1017/S0007114519002538 SN - 0007-1145 SN - 1475-2662 VL - 123 IS - 2 SP - 198 EP - 208 PB - Cambridge University Press CY - Cambridge ER - TY - GEN A1 - McNulty, Margaret A. A1 - Goupil, Brad A. A1 - Albarado, Diana C. A1 - Castaño-Martinez, Teresa A1 - Ambrosi, Thomas H. A1 - Puh, Spela A1 - Schulz, Tim Julius A1 - Schürmann, Annette A1 - Morrison, Christopher D. A1 - Laeger, Thomas T1 - FGF21, not GCN2, influences bone morphology due to dietary protein restrictions T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Background: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone. Methods: Adult wild-type (WT) or Fgf21 KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or Gcn2 KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (mu CT) for changes in trabecular and cortical architecture and mass. Results: In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of Fgf21 but not Gcn2. This decrease in bone did not appear after 2 weeks on the LP diet. In addition, Fgf21 KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture. Conclusions: This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1406 KW - dietary restriction KW - protein restriction KW - FGF21 KW - GCN2 KW - microcomputed tomography Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-516297 SN - 1866-8372 ER - TY - JOUR A1 - McNulty, Margaret A. A1 - Goupil, Brad A. A1 - Albarado, Diana C. A1 - Castaño-Martinez, Teresa A1 - Ambrosi, Thomas H. A1 - Puh, Spela A1 - Schulz, Tim Julius A1 - Schürmann, Annette A1 - Morrison, Christopher D. A1 - Laeger, Thomas T1 - FGF21, not GCN2, influences bone morphology due to dietary protein restrictions JF - Bone Reports N2 - Background: Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone. Methods: Adult wild-type (WT) or Fgf21 KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or Gcn2 KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (mu CT) for changes in trabecular and cortical architecture and mass. Results: In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of Fgf21 but not Gcn2. This decrease in bone did not appear after 2 weeks on the LP diet. In addition, Fgf21 KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture. Conclusions: This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21. KW - dietary restriction KW - protein restriction KW - FGF21 KW - GCN2 KW - microcomputed tomography Y1 - 2020 U6 - https://doi.org/10.1016/j.bonr.2019.100241 SN - 2352-1872 VL - 12 SP - 1 EP - 10 PB - Elsevier CY - Amsterdam ER - TY - GEN A1 - Naser, Eyad A1 - Kadow, Stephanie A1 - Schumacher, Fabian A1 - Mohamed, Zainelabdeen H. A1 - Kappe, Christian A1 - Hessler, Gabriele A1 - Pollmeier, Barbara A1 - Kleuser, Burkhard A1 - Arenz, Christoph A1 - Becker, Katrin Anne A1 - Gulbins, Erich A1 - Carpinteiro, Alexander T1 - Characterization of the small molecule ARC39 BT - a direct and specific inhibitor of acid sphingomyelinase in vitro[S] T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM's catalytic activity in cultured cells, a mechanism that differs from that of functional inhibitors of ASM. We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASM-promoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen, or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1407 KW - sphingolipids KW - sphingomyelin KW - cerami-des KW - lipid metabolism KW - enzymology KW - lysosome KW - lysosomal hydrolases KW - acid ceramidase KW - bisphosphonates KW - functional inhibitors of acid sphin-gomyelinase KW - 1-aminodecylidene bis-phosphonic acid Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-516635 SN - 1866-8372 IS - 6 ER - TY - JOUR A1 - Naser, Eyad A1 - Kadow, Stephanie A1 - Schumacher, Fabian A1 - Mohamed, Zainelabdeen H. A1 - Kappe, Christian A1 - Hessler, Gabriele A1 - Pollmeier, Barbara A1 - Kleuser, Burkhard A1 - Arenz, Christoph A1 - Becker, Katrin Anne A1 - Gulbins, Erich A1 - Carpinteiro, Alexander T1 - Characterization of the small molecule ARC39 BT - a direct and specific inhibitor of acid sphingomyelinase in vitro[S] JF - Journal of Lipid Research N2 - Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM's catalytic activity in cultured cells, a mechanism that differs from that of functional inhibitors of ASM. We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASM-promoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen, or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo. KW - sphingolipids KW - sphingomyelin KW - cerami-des KW - lipid metabolism KW - enzymology KW - lysosome KW - lysosomal hydrolases KW - acid ceramidase KW - bisphosphonates KW - functional inhibitors of acid sphin-gomyelinase KW - 1-aminodecylidene bis-phosphonic acid Y1 - 2021 U6 - https://doi.org/10.1194/jlr.RA120000682 SN - 1539-7262 SN - 0022-2275 VL - 61 IS - 6 SP - 896 EP - 910 PB - American Society for Biochemistry and Molecular Biology CY - Bethesda ER - TY - GEN A1 - Weber, Daniela A1 - Kochlik, Bastian A1 - Demuth, Ilja A1 - Steinhagen-Thiessen, Elisabeth A1 - Grune, Tilman A1 - Norman, Kristina T1 - Plasma carotenoids, tocopherols and retinol BT - Association with age in the Berlin Aging Study II T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1409 KW - carotenoids KW - tocopherols KW - micronutrients KW - age KW - plasma KW - food frequency questionnaire Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515996 SN - 1866-8372 ER - TY - JOUR A1 - Weber, Daniela A1 - Kochlik, Bastian A1 - Demuth, Ilja A1 - Steinhagen-Thiessen, Elisabeth A1 - Grune, Tilman A1 - Norman, Kristina T1 - Plasma carotenoids, tocopherols and retinol BT - Association with age in the Berlin Aging Study II JF - Redox Biology N2 - Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary. KW - carotenoids KW - tocopherols KW - micronutrients KW - age KW - plasma KW - food frequency questionnaire Y1 - 2020 U6 - https://doi.org/10.1016/j.redox.2020.101461 SN - 2213-2317 VL - 32 SP - 1 EP - 8 PB - Elsevier CY - Amsterdam ER - TY - GEN A1 - Olayide, Priscilla A1 - Large, Annabel A1 - Stridh, Linnea A1 - Rabbi, Ismail A1 - Baldermann, Susanne A1 - Stavolone, Livia A1 - Alexandersson, Erik T1 - Gene expression and metabolite profiling of thirteen Nigerian cassava landraces to elucidate starch and carotenoid composition T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The prevalence of vitamin A deficiency in sub-Saharan Africa necessitates effective approaches to improve provitamin A content of major staple crops. Cassava holds much promise for food security in sub-Saharan Africa, but a negative correlation between beta-carotene, a provitamin A carotenoid, and dry matter content has been reported, which poses a challenge to cassava biofortification by conventional breeding. To identify suitable material for genetic transformation in tissue culture with the overall aim to increase beta-carotene and maintain starch content as well as better understand carotenoid composition, root and leaf tissues from thirteen field-grown cassava landraces were analyzed for agronomic traits, carotenoid, chlorophyll, and starch content. The expression of five genes related to carotenoid biosynthesis were determined in selected landraces. Analysis revealed a weak negative correlation between starch and beta-carotene content, whereas there was a strong positive correlation between root yield and many carotenoids including beta-carotene. Carotenoid synthesis genes were expressed in both white and yellow cassava roots, but phytoene synthase 2 (PSY2), lycopene-epsilon-cyclase (LCY epsilon), and beta-carotenoid hydroxylase (CHY beta) expression were generally higher in yellow roots. This study identified lines with reasonably high content of starch and beta-carotene that could be candidates for biofortification by further breeding or plant biotechnological means. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1415 KW - carotenoid biosynthesis KW - ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) KW - provitamin A KW - biofortification Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-517834 SN - 1866-8372 IS - 3 ER - TY - JOUR A1 - Olayide, Priscilla A1 - Large, Annabel A1 - Stridh, Linnea A1 - Rabbi, Ismail A1 - Baldermann, Susanne A1 - Stavolone, Livia A1 - Alexandersson, Erik T1 - Gene expression and metabolite profiling of thirteen Nigerian cassava landraces to elucidate starch and carotenoid composition JF - Agronomy N2 - The prevalence of vitamin A deficiency in sub-Saharan Africa necessitates effective approaches to improve provitamin A content of major staple crops. Cassava holds much promise for food security in sub-Saharan Africa, but a negative correlation between beta-carotene, a provitamin A carotenoid, and dry matter content has been reported, which poses a challenge to cassava biofortification by conventional breeding. To identify suitable material for genetic transformation in tissue culture with the overall aim to increase beta-carotene and maintain starch content as well as better understand carotenoid composition, root and leaf tissues from thirteen field-grown cassava landraces were analyzed for agronomic traits, carotenoid, chlorophyll, and starch content. The expression of five genes related to carotenoid biosynthesis were determined in selected landraces. Analysis revealed a weak negative correlation between starch and beta-carotene content, whereas there was a strong positive correlation between root yield and many carotenoids including beta-carotene. Carotenoid synthesis genes were expressed in both white and yellow cassava roots, but phytoene synthase 2 (PSY2), lycopene-epsilon-cyclase (LCY epsilon), and beta-carotenoid hydroxylase (CHY beta) expression were generally higher in yellow roots. This study identified lines with reasonably high content of starch and beta-carotene that could be candidates for biofortification by further breeding or plant biotechnological means. KW - carotenoid biosynthesis KW - ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) KW - provitamin A KW - biofortification Y1 - 2020 U6 - https://doi.org/10.3390/agronomy10030424 SN - 2073-4395 VL - 10 IS - 3 SP - 1 EP - 16 PB - MDPI CY - Basel ER - TY - GEN A1 - Kessler, Katharina A1 - Hornemann, Silke A1 - Rudovich, Natalia A1 - Weber, Daniela A1 - Grune, Tilman A1 - Kramer, Achim A1 - Pfeiffer, Andreas F. H. A1 - Pivovarova-Ramich, Olga T1 - Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1425 KW - meal timing KW - saliva KW - circadian clock KW - adiponectin KW - resistin KW - visfatin KW - insulin KW - melatonin KW - cortisol KW - cytokines Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-512079 SN - 1866-8372 IS - 2 ER - TY - JOUR A1 - Kessler, Katharina A1 - Hornemann, Silke A1 - Rudovich, Natalia A1 - Weber, Daniela A1 - Grune, Tilman A1 - Kramer, Achim A1 - Pfeiffer, Andreas F. H. A1 - Pivovarova-Ramich, Olga T1 - Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers JF - Nutrients N2 - Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies. KW - meal timing KW - saliva KW - circadian clock KW - adiponectin KW - resistin KW - visfatin KW - insulin KW - melatonin KW - cortisol KW - cytokines Y1 - 2020 U6 - https://doi.org/10.3390/nu12020340 SN - 2072-6643 IS - 2 SP - 1 EP - 12 PB - MDPI CY - Basel ER - TY - GEN A1 - Schedlbauer, Carola A1 - Blaue, Dominique A1 - Raila, Jens A1 - Vervuert, Ingrid T1 - Alterations of serum vitamin E and vitamin A concentrations of ponies and horses during experimentally induced obesity T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum alpha-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (+/- SD) % BW gain achieved during two years of excess energy intake was 29.9 +/- 19.4% for ponies and 17 +/- 6.74% for horses. Serum alpha-tocopherol increased significantly in ponies and horses during excess energy intake and circulating alpha-tocopherol levels correlated positively with alpha-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1429 KW - body weight gain KW - equine KW - laminitis KW - retinol-binding protein 4 KW - α-tocophero Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-519515 SN - 1866-8372 IS - 5 ER - TY - CHAP A1 - Schenke, Maren A1 - Schjeide, Brit-Maren A1 - Püschel, Gerhard A1 - Seeger, Bettina T1 - Human motor neurons diffentiated from plutipotent stem cells as superior traged cells for botulinum neuotoxin potency testing BT - In: German Pharm-Tox Summit 2020: abstracts of the 86th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) T2 - Naunyn-Schmiedeberg's archives of pharmacology Y1 - 2020 U6 - https://doi.org/10.1007/s00210-020-01828-y SN - 0028-1298 SN - 1432-1912 VL - 393 IS - SUPPL 1 SP - 10 EP - 10 PB - Springer CY - Berlin ; Heidelberg ER - TY - JOUR A1 - Fink, Julian A1 - Schumacher, Fabian A1 - Schlegel, Jan A1 - Stenzel, Philipp A1 - Wigger, Dominik A1 - Sauer, Markus A1 - Kleuser, Burkhard A1 - Seibel, Jürgen T1 - Azidosphinganine enables metabolic labeling and detection of sphingolipid de novo synthesis JF - Organic & biomolecular chemistry : an international journal of synthetic, physical and biomolecular organic chemistry N2 - Here were report the combination of biocompatible click chemistry of omega-azidosphinganine with fluorescence microscopy and mass spectrometry as a powerful tool to elaborate the sphingolipid metabolism. The azide probe was efficiently synthesized over 13 steps starting from l-serine in an overall yield of 20% and was used for live-cell fluorescence imaging of the endoplasmic reticulum in living cells by bioorthogonal click reaction with a DBCO-labeled fluorophore revealing that the incorporated analogue is mainly localized in the endoplasmic membrane like the endogenous species. A LC-MS(/MS)-based microsomal in vitro assay confirmed that omega-azidosphinganine mimics the natural species enabling the identification and analysis of metabolic breakdown products of sphinganine as a key starting intermediate in the complex sphingolipid biosynthetic pathways. Furthermore, the sphinganine-fluorophore conjugate after click reaction was enzymatically tolerated to form its dihydroceramide and ceramide metabolites. Thus, omega-azidosphinganine represents a useful biofunctional tool for metabolic investigations both by in vivo fluorescence imaging of the sphingolipid subcellular localization in the ER and by in vitro high-resolution mass spectrometry analysis. This should reveal novel insights of the molecular mechanisms sphingolipids and their processing enzymes have e.g. in infection. Y1 - 2021 U6 - https://doi.org/10.1039/d0ob02592e SN - 1477-0520 SN - 1477-0539 VL - 19 IS - 10 SP - 2203 EP - 2212 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Bishop, Christopher Allen A1 - Machate, Tina A1 - Henning, Thorsten A1 - Henkel-Oberländer, Janin A1 - Püschel, Gerhard A1 - Weber, Daniela A1 - Grune, Tilman A1 - Klaus, Susanne A1 - Weitkunat, Karolin T1 - Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle JF - Nutrition & Diabetes N2 - Objective: Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake. Methods: To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes). Results: Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure-likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/ insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling. Conclusion: These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance. Y1 - 2022 U6 - https://doi.org/10.1038/s41387-022-00200-8 SN - 2044-4052 VL - 12 IS - 1 PB - Nature Publishing Group CY - London ER - TY - JOUR A1 - Nicolai, Merle Marie A1 - Witt, Barbara A1 - Friese, Sharleen A1 - Michaelis, Vivien A1 - Hölz-Armstrong, Lisa A1 - Martin, Maximilian A1 - Ebert, Franziska A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Mechanistic studies on the adverse effects of manganese overexposure in differentiated LUHMES cells JF - Food and chemical toxicology N2 - Manganese (Mn) is an essential trace element, but overexposure is associated with toxicity and neurological dysfunction. Accumulation of Mn can be observed in dopamine-rich regions of the brain in vivo and Mn-induced oxidative stress has been discussed extensively. Nevertheless, Mn-induced DNA damage, adverse effects of DNA repair, and possible resulting consequences for the neurite network are not yet characterized. For this, LUHMES cells were used, as they differentiate into dopaminergic-like neurons and form extensive neurite networks. Experiments were conducted to analyze Mn bioavailability and cytotoxicity of MnCl2, indicating a dose-dependent uptake and substantial cytotoxic effects. DNA damage, analyzed by means of 8-oxo-7,8-dihydro-2'-guanine (8oxodG) and single DNA strand break formation, showed significant dose- and time-dependent increase of DNA damage upon 48 h Mn exposure. Furthermore, the DNA damage response was increased which was assessed by analytical quantification of poly(ADP-ribosyl)ation (PARylation). Gene expression of the respective DNA repair genes was not significantly affected. Degradation of the neuronal network is significantly altered by 48 h Mn exposure. Altogether, this study contributes to the characterization of Mn-induced neurotoxicity, by analyzing the adverse effects of Mn on genome integrity in dopaminergic-like neurons and respective outcomes. KW - Manganese KW - Dopaminergic neurons KW - DNA integrity KW - DNA repair KW - Neurodegeneration KW - Oxidative stress KW - Genotoxicity Y1 - 2022 U6 - https://doi.org/10.1016/j.fct.2022.112822 SN - 0278-6915 SN - 1873-6351 VL - 161 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Klaus, Susanne A1 - Igual Gil, Carla A1 - Ost, Mario T1 - Regulation of diurnal energy balance by mitokines JF - Cellular and molecular life sciences : CMLS N2 - The mammalian system of energy balance regulation is intrinsically rhythmic with diurnal oscillations of behavioral and metabolic traits according to the 24 h day/night cycle, driven by cellular circadian clocks and synchronized by environmental or internal cues such as metabolites and hormones associated with feeding rhythms. Mitochondria are crucial organelles for cellular energy generation and their biology is largely under the control of the circadian system. Whether mitochondrial status might also feed-back on the circadian system, possibly via mitokines that are induced by mitochondrial stress as endocrine-acting molecules, remains poorly understood. Here, we describe our current understanding of the diurnal regulation of systemic energy balance, with focus on fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), two well-known endocrine-acting metabolic mediators. FGF21 shows a diurnal oscillation and directly affects the output of the brain master clock. Moreover, recent data demonstrated that mitochondrial stress-induced GDF15 promotes a day-time restricted anorexia and systemic metabolic remodeling as shown in UCP1-transgenic mice, where both FGF21 and GDF15 are induced as myomitokines. In this mouse model of slightly uncoupled skeletal muscle mitochondria GDF15 proved responsible for an increased metabolic flexibility and a number of beneficial metabolic adaptations. However, the molecular mechanisms underlying energy balance regulation by mitokines are just starting to emerge, and more data on diurnal patterns in mouse and man are required. This will open new perspectives into the diurnal nature of mitokines and action both in health and disease. KW - Mitochondria KW - FGF21 KW - GDF15 KW - Circadian rhythm KW - Hormones KW - Nutrition Y1 - 2021 U6 - https://doi.org/10.1007/s00018-020-03748-9 SN - 1420-682X SN - 1420-9071 VL - 78 IS - 7 SP - 3369 EP - 3384 PB - Springer International Publishing AG CY - Cham (ZG) ER - TY - JOUR A1 - Schweigert, Florian J. ED - Kollodzeiski, Ulrike ED - Hafner, Johann Evangelist T1 - Hässlich aber gut BT - Insekten als Nahrungsmittel – Warum wir uns ekeln JF - Du sollst nicht essen: Warum Menschen auf Nahrung verzichten – interdisziplinäre Zugänge Y1 - 2024 SN - 978-3-98740-007-0 SN - 978-3-98740-008-7 U6 - https://doi.org/10.5771/9783987400087 SP - 47 EP - 59 PB - Ergon Verlag CY - Baden-Baden ER - TY - GEN A1 - Kollodzeiski, Ulrike A1 - Hafner, Johann Evangelist A1 - Lippert, Rachel N. A1 - Bartelmeß, Tina A1 - Schweigert, Florian J. A1 - Bigalke, Bernadett A1 - Krochmalnik, Daniel A1 - Sancı, Kadir A1 - Kardas, Arhan A1 - Dietzel, Irene A1 - Yilmaz, Rümeysa A1 - Olhoeft, Netanel A1 - Struß, Lukas ED - Kollodzeiski, Ulrike ED - Hafner, Johann Evangelist T1 - Du sollst nicht essen BT - Warum Menschen auf Nahrung verzichten – interdisziplinäre Zugänge T2 - Zweitveröffentlichungen der Universität Potsdam : Philosophische Reihe N2 - Zwar sind Menschen biologisch gesehen Allesesser, dennoch gibt es keine Gemeinschaft, die alle ihr zur Verfügung stehenden Nahrungsmittel voll ausschöpft. Immer wird etwas nicht gegessen. Warum wir nicht essen, was wir nicht essen – das beleuchtet dieser Sammelband aus neuro-, ernährungs-, gesellschafts- und religionswissenschaftlicher Perspektive. Ein „religiöser Nutriscore“ gibt Auskunft über die wichtigsten Verzichtsregeln in Judentum, Christentum und Islam. Eine Fotostrecke veranschaulicht, wie bestimmte Speisen zu Festen und Feiertagen zu einem heiligen Essen werden. Nicht zuletzt werden Wege aufgezeigt, wie Menschen, die verschiedene Speiseregeln befolgen, dennoch zusammen essen können – inklusive Praxistest in der Unimensa. T3 - Zweitveröffentlichungen der Universität Potsdam : Philosophische Reihe - 191 KW - Speisegebot KW - Ernährungsgewohnheit KW - Religiöses Leben KW - Judentum KW - Christentum KW - Islam Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-627542 SN - 1866-8380 IS - 191 EP - 172 ER - TY - BOOK A1 - Kollodzeiski, Ulrike A1 - Hafner, Johann Evangelist A1 - Lippert, Rachel N. A1 - Bartelmeß, Tina A1 - Schweigert, Florian J. A1 - Bigalke, Bernadett A1 - Krochmalnik, Daniel A1 - Sancı, Kadir A1 - Kardas, Arhan A1 - Dietzel, Irene A1 - Yilmaz, Rümeysa A1 - Olhoeft, Netanel A1 - Struß, Lukas ED - Kollodzeiski, Ulrike ED - Hafner, Johann Evangelist T1 - Du sollst nicht essen BT - Warum Menschen auf Nahrung verzichten – interdisziplinäre Zugänge N2 - Zwar sind Menschen biologisch gesehen Allesesser, dennoch gibt es keine Gemeinschaft, die alle ihr zur Verfügung stehenden Nahrungsmittel voll ausschöpft. Immer wird etwas nicht gegessen. Warum wir nicht essen, was wir nicht essen – das beleuchtet dieser Sammelband aus neuro-, ernährungs-, gesellschafts- und religionswissenschaftlicher Perspektive. Ein „religiöser Nutriscore“ gibt Auskunft über die wichtigsten Verzichtsregeln in Judentum, Christentum und Islam. Eine Fotostrecke veranschaulicht, wie bestimmte Speisen zu Festen und Feiertagen zu einem heiligen Essen werden. Nicht zuletzt werden Wege aufgezeigt, wie Menschen, die verschiedene Speiseregeln befolgen, dennoch zusammen essen können – inklusive Praxistest in der Unimensa. KW - Speisegebot KW - Ernährungsgewohnheit KW - Religiöses Leben KW - Judentum KW - Christentum KW - Islam Y1 - 2024 SN - 978-3-98740-007-0 SN - 978-3-98740-008-7 U6 - https://doi.org/10.5771/9783987400087 EP - 172 PB - Ergon Verlag CY - Baden-Baden ER - TY - JOUR A1 - Burkhardt, Wiebke A1 - Rausch, Theresa A1 - Klopfleisch, Robert A1 - Blaut, Michael A1 - Braune, Annett T1 - Impact of dietary sulfolipid-derived sulfoquinovose on gut microbiota composition and inflammatory status of colitis-prone interleukin-10-deficient mice JF - International journal of medical microbiology : IJMM N2 - The interplay between diet, intestinal microbiota and host is a major factor impacting health. A diet rich in unsaturated fatty acids has been reported to stimulate the growth of Bilophila wadsworthia by increasing the proportion of the sulfonated bile acid taurocholate (TC). The taurine-induced overgrowth of B. wadsworthia promoted the development of colitis in interleukin-10-deficient (IL-10(-/-)) mice. This study aimed to investigate whether intake of the sulfonates sulfoquinovosyl diacylglycerols (SQDG) with a dietary supplement or their degradation product sulfoquinovose (SQ), stimulate the growth of B. wadsworthia in a similar manner and, thereby, cause intestinal inflammation. Conventional IL-10(-/-) mice were fed a diet supplemented with the SQDG-rich cyanobacterium Arthrospira platensis (Spirulina). SQ or TC were orally applied to conventional IL-10(-/-) mice and gnotobiotic IL-10(-/-) mice harboring a simplified human intestinal microbiota with or without B. wadsworthia. Analyses of inflammatory parameters revealed that none of the sulfonates induced severe colitis, but both, Spirulina and TC, induced expression of pro-inflammatory cytokines in cecal mucosa. Cell numbers of B. wadsworthia decreased almost two orders of magnitude by Spirulina feeding but slightly increased in gnotobiotic SQ and conventional TC mice. Changes in microbiota composition were observed in feces as a result of Spirulina or TC feeding in conventional mice. In conclusion, the dietary sulfonates SQDG and their metabolite SQ did not elicit bacteria-induced intestinal inflammation in IL-10(-/-) mice and, thus, do not promote colitis. KW - Sulfonate KW - Sulfoquinovose KW - Spirulina KW - Inflammatory bowel disease KW - Bilophila wadsworthia KW - Taurocholate Y1 - 2021 U6 - https://doi.org/10.1016/j.ijmm.2021.151494 SN - 1618-0607 VL - 311 IS - 3 PB - Elsevier CY - München ER - TY - GEN A1 - Rodríguez Sillke, Yasmina A1 - Schumann, Michael A1 - Lissner, Donata A1 - Branchi, Frederica A1 - Glauben, Rainer A1 - Siegmund, Britta T1 - Small intestinal inflammation but not colitis drives pro-inflammatory nutritional antigen-specific T-cell response T2 - Journal of Crohn's and Colitis N2 - Background: Inflammatory bowel disease (IBD) represents a dysregulation of the mucosal immune system. The pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC) is linked to the loss of intestinal tolerance and barrier function. The healthy mucosal immune system has previously been shown to be inert against food antigens. Since the small intestine is the main contact surface for antigens and therefore the immunological response, the present study served to analyse food-antigen-specific T cells in the peripheral blood of IBD patients. Methods: Peripheral blood mononuclear cells of CD, with an affected small intestine, and UC (colitis) patients, either active or in remission, were stimulated with the following food antigens: gluten, soybean, peanut and ovalbumin. Healthy controls and celiac disease patients were included as controls. Antigen-activated CD4+ T cells in the peripheral blood were analysed by a magnetic enrichment of CD154+ effector T cells and a cytometric antigen-reactive T-cell analysis (‘ARTE’ technology) followed by characterisation of the ef- fector response. Results: The effector T-cell response of antigen-specific T cells were compared between CD with small intestinal inflammation and UC where inflammation was restricted to the colon. Among all tested food antigens, the highest frequency of antigen-specific T cells (CD4+CD154+) was found for gluten. Celiac disease patients were included as control, since gluten has been identified as the disease- causing antigen. The highest frequency of gluten antigen-specific T cells was revealed in active CD when compared with UC, celiac disease on a gluten-free diet (GFD) and healthy controls. Ovalbuminspecific T cells were almost undetectable, whereas the reaction to soybean and peanut was slightly higher. But again, the strong- est reaction was observed in CD with small intestinal involvement compared with UC. Remarkably, in celiac disease on a GFD only antigen-specific cells for gluten were detected. These gluten-specific T cells were characterised by up-regulation of the pro-inflammatory cytokines IFN-γ, IL-17A and TNF-α. IFN-g was exclusively elevated in CD patients with active disease. Gluten-specific T-cells expressing IL-17A were increased in all IBD patients. Furthermore, T cells of CD patients, independent of disease activity, revealed a high expression of the pro-inflammatory cytokine TNF-α. Conclusion: The ‘ARTE’-technique allows to analyse and quantify food antigen specific T cells in the peripheral blood of IBD patients indicating a potential therapeutic insight. These data provide evidence that small intestinal inflammation in CD is key for the development of a systemic pro-inflammatory effector T-cell response driven by food antigens. Y1 - 2020 U6 - https://doi.org/10.1093/ecco-jcc/jjz203.172 SN - 1873-9946 SN - 1876-4479 VL - 14 SP - S154 EP - S155 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Volk, Christin A1 - Brandsch, Corinna A1 - Schlegelmilch, Ulf A1 - Wensch-Dorendorf, Monika A1 - Hirche, Frank A1 - Simm, Andreas A1 - Gargum, Osama A1 - Wiacek, Claudia A1 - Braun, Peggy G. A1 - Kopp, Johannes F. A1 - Schwerdtle, Tanja A1 - Treede, Hendrik A1 - Stangl, Gabriele I. T1 - Postprandial metabolic response to rapeseed protein in healthy subjects JF - Nutrients N2 - Plant proteins have become increasingly important for ecological reasons. Rapeseed is a novel source of plant proteins with high biological value, but its metabolic impact in humans is largely unknown. A randomized, controlled intervention study including 20 healthy subjects was conducted in a crossover design. All participants received a test meal without additional protein or with 28 g of rapeseed protein isolate or soy protein isolate (control). Venous blood samples were collected over a 360-min period to analyze metabolites; satiety was assessed using a visual analog scale. Postprandial levels of lipids, urea, and amino acids increased following the intake of both protein isolates. The postprandial insulin response was lower after consumption of the rapeseed protein than after intake of the soy protein (p< 0.05), whereas the postmeal responses of glucose, lipids, interleukin-6, minerals, and urea were comparable between the two protein isolates. Interestingly, the rapeseed protein exerted stronger effects on postprandial satiety than the soy protein (p< 0.05). The postmeal metabolism following rapeseed protein intake is comparable with that of soy protein. The favorable effect of rapeseed protein on postprandial insulin and satiety makes it a valuable plant protein for human nutrition. KW - rapeseed protein KW - soy protein KW - postprandial study KW - metabolic response KW - healthy subjects Y1 - 2020 U6 - https://doi.org/10.3390/nu12082270 SN - 2072-6643 VL - 12 IS - 8 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schulze, Matthias Bernd T1 - Dietary linoleic acid: will modifying dietary fat quality reduce the risk of type 2 diabetes? JF - Diabetes care Y1 - 2021 U6 - https://doi.org/10.2337/dci21-0031 SN - 0149-5992 SN - 1935-5548 VL - 44 IS - 9 SP - 1913 EP - 1915 PB - American Diabetes Association CY - Alexandria ER - TY - CHAP A1 - Schenke, Maren A1 - Schjeide, Brit-Maren A1 - Püschel, Gerhard Paul A1 - Seeger, Bettina T1 - Serotype-specific sensitivity to Botulinum neurotoxins of iPSC-derived motor neurons T2 - Naunyn-Schmiedeberg's archives of pharmacology Y1 - 2021 U6 - https://doi.org/10.1007/s00210-021-02066-6 SN - 0028-1298 SN - 1432-1912 VL - 394 IS - Suppl. 1 SP - S4 EP - S4 PB - Springer CY - Berlin ; Heidelberg ER - TY - JOUR A1 - Jannasch, Franziska A1 - Nickel, Daniela V. A1 - Bergmann, Manuela M. A1 - Schulze, Matthias Bernd T1 - A new evidence-based diet score to capture associations of food consumption and chronic disease risk JF - Nutrients / Molecular Diversity Preservation International (MDPI) N2 - Previously, the attempt to compile German dietary guidelines into a diet score was predominantly not successful with regards to preventing chronic diseases in the EPIC-Potsdam study. Current guidelines were supplemented by the latest evidence from systematic reviews and expert papers published between 2010 and 2020 on the prevention potential of food groups on chronic diseases such as type 2 diabetes, cardiovascular diseases and cancer. A diet score was developed by scoring the food groups according to a recommended low, moderate or high intake. The relative validity and reliability of the diet score, assessed by a food frequency questionnaire, was investigated. The consideration of current evidence resulted in 10 key food groups being preventive of the chronic diseases of interest. They served as components in the diet score and were scored from 0 to 1 point, depending on their recommended intake, resulting in a maximum of 10 points. Both the reliability (r = 0.53) and relative validity (r = 0.43) were deemed sufficient to consider the diet score as a stable construct in future investigations. This new diet score can be a promising tool to investigate dietary intake in etiological research by concentrating on 10 key dietary determinants with evidence-based prevention potential for chronic diseases. KW - diet score KW - dietary guidelines KW - food groups KW - chronic disease KW - type 2 KW - diabetes KW - cardiovascular disease KW - cancer KW - prevention KW - reliability; KW - validity Y1 - 2022 U6 - https://doi.org/10.3390/nu14112359 SN - 2072-6643 VL - 14 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Xiong, Chan A1 - Stiboller, Michael A1 - Glabonjat, Ronald A. A1 - Rieger, Jaqueline A1 - Paton, Lhiam A1 - Francesconi, Kevin A. T1 - Transport of arsenolipids to the milk of a nursing mother after consuming salmon fish JF - Journal of trace elements in medicine and biology N2 - Objective: We address two questions relevant to infants' exposure to potentially toxic arsenolipids, namely, are the arsenolipids naturally present in fish transported intact to a mother's milk, and what is the efficiency of this transport. Methods: We investigated the transport of arsenolipids and other arsenic species present in fish to mother's milk by analyzing the milk of a single nursing mother at 15 sampling times over a 3-day period after she had consumed a meal of salmon. Total arsenic values were obtained by elemental mass spectrometry, and arsenic species were measured by HPLC coupled to both elemental and molecular mass spectrometry. Results: Total arsenic increased from background levels (0.1 mu g As kg(-1)) to a peak value of 1.72 lig As kg(-1) eight hours after the fish meal. The pattern for arsenolipids was similar to that of total arsenic, increasing from undetectable background levels (< 0.01 mu g As kg(-1)) to a peak after eight hours of 0.45 mu g As kg(-1). Most of the remaining total arsenic in the milk was accounted for by arsenobetaine. The major arsenolipids in the salmon were arsenic hydrocarbons (AsHCs; 55 % of total arsenolipids), and these compounds were also the dominant arsenolipids in the milk where they contributed over 90 % of the total arsenolipids. Conclusions: Our study has shown that ca 2-3 % of arsenic hydrocarbons, natural constituents of fish, can be directly transferred unchanged to the milk of a nursing mother. In view of the potential neurotoxicity of AsHCs, the effects of these compounds on the brain developmental stage of infants need to be investigated. KW - human milk KW - arsenolipids KW - salmon fish KW - HPLC/ICPMS KW - HPLC/HR-ESMS Y1 - 2020 U6 - https://doi.org/10.1016/j.jtemb.2020.126502 SN - 0946-672X VL - 61 PB - Elsevier CY - München ER - TY - JOUR A1 - Gellner, Anne-Kathrin A1 - Sitter, Aileen A1 - Rackiewicz, Michal A1 - Sylvester, Marc A1 - Philipsen, Alexandra A1 - Zimmer, Andreas A1 - Stein, Valentin T1 - Stress vulnerability shapes disruption of motor cortical neuroplasticity JF - Translational Psychiatry N2 - Chronic stress is a major cause of neuropsychiatric conditions such as depression. Stress vulnerability varies individually in mice and humans, measured by behavioral changes. In contrast to affective symptoms, motor retardation as a consequence of stress is not well understood. We repeatedly imaged dendritic spines of the motor cortex in Thy1-GFP M mice before and after chronic social defeat stress. Susceptible and resilient phenotypes were discriminated by symptom load and their motor learning abilities were assessed by a gross and fine motor task. Stress phenotypes presented individual short- and long-term changes in the hypothalamic-pituitary-adrenal axis as well as distinct patterns of altered motor learning. Importantly, stress was generally accompanied by a marked reduction of spine density in the motor cortex and spine dynamics depended on the stress phenotype. We found astrogliosis and altered microglia morphology along with increased microglia-neuron interaction in the motor cortex of susceptible mice. In cerebrospinal fluid, proteomic fingerprints link the behavioral changes and structural alterations in the brain to neurodegenerative disorders and dysregulated synaptic homeostasis. Our work emphasizes the importance of synaptic integrity and the risk of neurodegeneration within depression as a threat to brain health. Y1 - 2022 U6 - https://doi.org/10.1038/s41398-022-01855-8 SN - 2158-3188 VL - 12 IS - 1 PB - Nature Publishing Group CY - London ER - TY - JOUR A1 - Stepanovska, Bisera A1 - Zivkovic, Aleksandra A1 - Enzmann, Gaby A1 - Tietz, Silvia A1 - Homann, Thomas A1 - Kleuser, Burkhard A1 - Engelhardt, Britta A1 - Stark, Holger A1 - Huwiler, Andrea T1 - Morpholino analogues of fingolimod as novel and selective S1P1 ligands with in vivo efficacy in a mouse model of experimental antigen-induced encephalomyelitis JF - International journal of molecular sciences N2 - Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system (CNS) which is associated with lower life expectancy and disability. The experimental antigen-induced encephalomyelitis (EAE) in mice is a useful animal model of MS, which allows exploring the etiopathogenetic mechanisms and testing novel potential therapeutic drugs. A new therapeutic paradigm for the treatment of MS was introduced in 2010 through the sphingosine 1-phosphate (S1P) analogue fingolimod (FTY720, Gilenya(R)), which acts as a functional S1P(1) antagonist on T lymphocytes to deplete these cells from the blood. In this study, we synthesized two novel structures, ST-1893 and ST-1894, which are derived from fingolimod and chemically feature a morpholine ring in the polar head group. These compounds showed a selective S1P(1) activation profile and a sustained S1P(1) internalization in cultures of S1P(1)-overexpressing Chinese hamster ovary (CHO)-K1 cells, consistent with a functional antagonism. In vivo, both compounds induced a profound lymphopenia in mice. Finally, these substances showed efficacy in the EAE model, where they reduced clinical symptoms of the disease, and, on the molecular level, they reduced the T-cell infiltration and several inflammatory mediators in the brain and spinal cord. In summary, these data suggest that S1P(1)-selective compounds may have an advantage over fingolimod and siponimod, not only in MS but also in other autoimmune diseases. KW - ST-1893 KW - ST-1894 KW - morpholino analogues of fingolimod KW - sphingosine KW - 1-phosphate KW - immunomodulator KW - lymphopenia KW - multiple sclerosis KW - experimental antigen-induced encephalomyelitis Y1 - 2020 U6 - https://doi.org/10.3390/ijms21186463 SN - 1422-0067 VL - 21 IS - 18 PB - MDPI CY - Basel ER - TY - JOUR A1 - Birukov, Anna A1 - Cuadrat, Rafael R. C. A1 - Polemiti, Elli A1 - Eichelmann, Fabian A1 - Schulze, Matthias Bernd T1 - Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals BT - a cross-sectional study JF - Cardiovascular diabetology N2 - Background Advanced glycation end-products are proteins that become glycated after contact with sugars and are implicated in endothelial dysfunction and arterial stiffening. We aimed to investigate the relationships between advanced glycation end-products, measured as skin autofluorescence, and vascular stiffness in various glycemic strata. Methods We performed a cross-sectional analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, comprising n = 3535 participants (median age 67 years, 60% women). Advanced glycation end-products were measured as skin autofluorescence with AGE-Reader (TM), vascular stiffness was measured as pulse wave velocity, augmentation index and ankle-brachial index with Vascular Explorer (TM). A subset of 1348 participants underwent an oral glucose tolerance test. Participants were sub-phenotyped into normoglycemic, prediabetes and diabetes groups. Associations between skin autofluorescence and various indices of vascular stiffness were assessed by multivariable regression analyses and were adjusted for age, sex, measures of adiposity and lifestyle, blood pressure, prevalent conditions, medication use and blood biomarkers. Results Skin autofluorescence associated with pulse wave velocity, augmentation index and ankle-brachial index, adjusted beta coefficients (95% CI) per unit skin autofluorescence increase: 0.38 (0.21; 0.55) for carotid-femoral pulse wave velocity, 0.25 (0.14; 0.37) for aortic pulse wave velocity, 1.00 (0.29; 1.70) for aortic augmentation index, 4.12 (2.24; 6.00) for brachial augmentation index and - 0.04 (- 0.05; - 0.02) for ankle-brachial index. The associations were strongest in men, younger individuals and were consistent across all glycemic strata: for carotid-femoral pulse wave velocity 0.36 (0.12; 0.60) in normoglycemic, 0.33 (- 0.01; 0.67) in prediabetes and 0.45 (0.09; 0.80) in diabetes groups; with similar estimates for aortic pulse wave velocity. Augmentation index was associated with skin autofluorescence only in normoglycemic and diabetes groups. Ankle-brachial index inversely associated with skin autofluorescence across all sex, age and glycemic strata. Conclusions Our findings indicate that advanced glycation end-products measured as skin autofluorescence might be involved in vascular stiffening independent of age and other cardiometabolic risk factors not only in individuals with diabetes but also in normoglycemic and prediabetic conditions. Skin autofluorescence might prove as a rapid and non-invasive method for assessment of macrovascular disease progression across all glycemic strata. KW - Advanced glycation end-products KW - AGE KW - Ankle-brachial index KW - Augmentation KW - index KW - Prediabetes KW - Glycemia KW - Pulse wave velocity KW - Skin KW - autofluorescence KW - Vascular stiffness Y1 - 2021 U6 - https://doi.org/10.1186/s12933-021-01296-5 SN - 1475-2840 VL - 20 IS - 1 PB - BioMed Central CY - London ER - TY - JOUR A1 - Pedro Ernesto, Pinho Tavares Leal A1 - da Silva, Alexandre Alves A1 - Rocha-Gomes, Arthur A1 - Riul, Tania Regina A1 - Cunha, Rennan Augusto A1 - Reichetzeder, Christoph A1 - Villela, Daniel Campos T1 - High-salt diet in the pre- and postweaning periods leads to amygdala oxidative stress and changes in locomotion and anxiety-like behaviors of male wistar rats JF - Frontiers in behavioral neuroscience N2 - High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)-offspring of standard diet fed dams who received a standard diet after weaning (n = 9-11), control-HS (C-HS)-offspring of standard diet fed dams who received a HS diet after weaning (n = 9-11), HS-C-offspring of HS diet fed dams who received a standard diet after weaning (n = 9-11), and HS-HS-offspring of HS diet fed dams who received a HS diet after weaning (n = 9-11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors. KW - high-sodium KW - open-field KW - elevated plus-maze KW - pre-natal KW - post-natal KW - redox state Y1 - 2022 U6 - https://doi.org/10.3389/fnbeh.2021.779080 SN - 1662-5153 VL - 15 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Aga-Barfknecht, Heja A1 - Soultoukis, George A. A1 - Stadion, Mandy A1 - Garcia-Carrizo, Francisco A1 - Jähnert, Markus A1 - Gottmann, Pascal A1 - Vogel, Heike A1 - Schulz, Tim Julius A1 - Schürmann, Annette T1 - Distinct adipogenic and fibrogenic differentiation capacities of mesenchymal stromal cells from pancreas and white adipose tissue JF - International journal of molecular sciences N2 - Pancreatic steatosis associates with beta-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals. KW - MSCs KW - fatty pancreas KW - WAT KW - lineage commitment KW - transcriptomics KW - miRNAs Y1 - 2022 U6 - https://doi.org/10.3390/ijms23042108 SN - 1422-0067 VL - 23 IS - 4 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Knoche, Lisa A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - LC-HRMS-Based identification of transformation products of the drug salinomycin generated by electrochemistry and liver microsome JF - Antibiotics N2 - The drug salinomycin (SAL) is a polyether antibiotic and used in veterinary medicine as coccidiostat and growth promoter. Recently, SAL was suggested as a potential anticancer drug. However, transformation products (TPs) resulting from metabolic and environmental degradation of SAL are incompletely known and structural information is missing. In this study, we therefore systematically investigated the formation and identification of SAL derived TPs using electrochemistry (EC) in an electrochemical reactor and rat and human liver microsome incubation (RLM and HLM) as TP generating methods. Liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) was applied to determine accurate masses in a suspected target analysis to identify TPs and to deduce occurring modification reactions of derived TPs. A total of 14 new, structurally different TPs were found (two EC-TPs, five RLM-TPs, and 11 HLM-TPs). The main modification reactions are decarbonylation for EC-TPs and oxidation (hydroxylation) for RLM/HLM-TPs. Of particular interest are potassium-based TPs identified after liver microsome incubation because these might have been overlooked or declared as oxidated sodium adducts in previous, non-HRMS-based studies due to the small mass difference between K and O + Na of 21 mDa. The MS fragmentation pattern of TPs was used to predict the position of identified modifications in the SAL molecule. The obtained knowledge regarding transformation reactions and novel TPs of SAL will contribute to elucidate SAL-metabolites with regards to structural prediction. KW - salinomycin KW - ionophore antibiotics KW - transformation product KW - electrochemistry KW - rat KW - human liver microsomes KW - HRMS Y1 - 2022 U6 - https://doi.org/10.3390/antibiotics11020155 SN - 2079-6382 VL - 11 IS - 2 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schiborn, Catarina A1 - Schulze, Matthias Bernd T1 - Precision prognostics for the development of complications in diabetes JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Individuals with diabetes face higher risks for macro- and microvascular complications than their non-diabetic counterparts. The concept of precision medicine in diabetes aims to optimise treatment decisions for individual patients to reduce the risk of major diabetic complications, including cardiovascular outcomes, retinopathy, nephropathy, neuropathy and overall mortality. In this context, prognostic models can be used to estimate an individual's risk for relevant complications based on individual risk profiles. This review aims to place the concept of prediction modelling into the context of precision prognostics. As opposed to identification of diabetes subsets, the development of prediction models, including the selection of predictors based on their longitudinal association with the outcome of interest and their discriminatory ability, allows estimation of an individual's absolute risk of complications. As a consequence, such models provide information about potential patient subgroups and their treatment needs. This review provides insight into the methodological issues specifically related to the development and validation of prediction models for diabetes complications. We summarise existing prediction models for macro- and microvascular complications, commonly included predictors, and examples of available validation studies. The review also discusses the potential of non-classical risk markers and omics-based predictors. Finally, it gives insight into the requirements and challenges related to the clinical applications and implementation of developed predictions models to optimise medical decision making. KW - Cardiovascular diseases KW - Complications in diabetes KW - Macrovascular KW - complications KW - Microvascular complications KW - Personalised medicine KW - Precision medicine KW - Precision prognostics KW - Review KW - Risk prediction KW - Risk KW - scores Y1 - 2022 U6 - https://doi.org/10.1007/s00125-022-05731-4 SN - 0012-186X SN - 1432-0428 PB - Springer CY - New York ER - TY - JOUR A1 - Solger, Franziska A1 - Kunz, Tobias C. A1 - Fink, Julian A1 - Paprotka, Kerstin A1 - Pfister, Pauline A1 - Hagen, Franziska A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Seibel, Jürgen A1 - Rudel, Thomas T1 - A role of sphingosine in the intracellular survival of Neisseria gonorrhoeae JF - Frontiers in Cellular and Infection Microbiology N2 - Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. Here, we investigated the role of sphingosine in the invasion and intracellular survival of gonococci. Sphingosine exhibited an anti-gonococcal activity in vitro. We used specific sphingosine analogs and click chemistry to visualize sphingosine in infected cells. Sphingosine localized to the membrane of intracellular gonococci. Inhibitor studies and the application of a sphingosine derivative indicated that increased sphingosine levels reduced the intracellular survival of gonococci. We demonstrate here, that sphingosine can target intracellular bacteria and may therefore exert a direct bactericidal effect inside cells. KW - Neisseria gonorrhoeae KW - sphingosine KW - sphingolipids KW - sphingosine kinases KW - invasion KW - survival KW - click chemistry Y1 - 2020 U6 - https://doi.org/10.3389/fcimb.2020.00215 SN - 2235-2988 VL - 10 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Fechner, Carolin A1 - Hackethal, Christin A1 - Höpfner, Tobias A1 - Dietrich, Jessica A1 - Bloch, Dorit A1 - Lindtner, Oliver A1 - Sarvan, Irmela T1 - Results of the BfR MEAL Study BT - in Germany, mercury is mostly contained in fish and seafood while cadmium, lead, and nickel are present in a broad spectrum of foods JF - Food chemistry: X N2 - The BfR MEAL Study provides representative levels of substances in foods consumed in Germany. Mercury, cadmium, lead, and nickel are contaminants present in foods introduced by environmental and industrial processes. Levels of these elements were investigated in 356 foods. Foods were purchased representatively, prepared as consumed and pooled with similar foods before analysis. Highest mean levels of mercury were determined in fish and seafood, while high levels of cadmium, lead, and nickel were present in cocoa products and legumes, nuts, oilseeds, and spices. The sampling by region, season, and production type showed minor differences in element levels for specific foods, however no tendency over all foods or for some food groups was apparent. The data on mercury, cadmium, lead, and nickel provide a comprehensive basis for chronic dietary exposure assessment of the population in Germany. All levels found were below regulated maximum levels. KW - Total diet study KW - BfR MEAL Study KW - Metals KW - Contaminants KW - Unprepared and KW - prepared foods KW - Regionality KW - Seasonality KW - Organic and conventional type of production Y1 - 2022 U6 - https://doi.org/10.1016/j.fochx.2022.100326 SN - 2590-1575 VL - 14 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Witt, Barbara A1 - Stiboller, Michael A1 - Raschke, Stefanie A1 - Friese, Sharleen A1 - Ebert, Franziska A1 - Schwerdtle, Tanja T1 - Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers JF - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS N2 - Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases. KW - Copper KW - Astrocytes KW - Toxicity KW - Mitochondria KW - ROS KW - Trace elements Y1 - 2021 U6 - https://doi.org/10.1016/j.jtemb.2021.126711 SN - 1878-3252 VL - 65 PB - Elsevier CY - München ER - TY - JOUR A1 - Schell, Mareike A1 - Wardelmann, Kristina A1 - Kleinridders, Andre T1 - Untangling the effect of insulin action on brain mitochondria and metabolism JF - Journal of neuroendocrinology N2 - The regulation of energy homeostasis is controlled by the brain and, besides requiring high amounts of energy, it relies on functional insulin/insulin-like growth factor (IGF)-1 signalling in the central nervous system. This energy is mainly provided by mitochondria in form of ATP. Thus, there is an intricate interplay between mitochondrial function and insulin/IGF-1 action to enable functional brain signalling and, accordingly, propagate a healthy metabolism. To adapt to different nutritional conditions, the brain is able to sense the current energy status via mitochondrial and insulin signalling-dependent pathways and exerts an appropriate metabolic response. However, regional, cell type and receptor-specific consequences of this interaction occur and are linked to diverse outcomes such as altered nutrient sensing, body weight regulation or even cognitive function. Impairments of this cross-talk can lead to obesity and glucose intolerance and are linked to neurodegenerative diseases, yet they also induce a self-sustainable, dysfunctional 'metabolic triangle' characterised by insulin resistance, mitochondrial dysfunction and inflammation in the brain. The identification of causal factors deteriorating insulin action, mitochondrial function and concomitantly a signature of metabolic stress in the brain is of utter importance to offer novel mechanistic insights into development of the continuously rising prevalence of non-communicable diseases such as type 2 diabetes and neurodegeneration. This review aims to determine the effect of insulin action on brain mitochondrial function and energy metabolism. It precisely outlines the interaction and differences between insulin action, insulin-like growth factor (IGF)-1 signalling and mitochondrial function; distinguishes between causality and association; and reveals its consequences for metabolism and cognition. We hypothesise that an improvement of at least one signalling pathway can overcome the vicious cycle of a self-perpetuating metabolic dysfunction in the brain present in metabolic and neurodegenerative diseases. KW - brain KW - energy homeostasis KW - inflammation KW - insulin signalling KW - metabolism KW - mitochondrial function Y1 - 2021 U6 - https://doi.org/10.1111/jne.12932 SN - 0953-8194 SN - 1365-2826 VL - 33 IS - 4 PB - Wiley CY - Hoboken ER - TY - CHAP A1 - Wandt, Viktoria Klara Veronika A1 - Winkelbeiner, Nicola A1 - Loßow, Kristina A1 - Kopp, Johannes A1 - Simon, Luise A1 - Ebert, Franziska A1 - Kipp, Anna Patricia A1 - Schwerdtle, Tanja T1 - Trace elements, ageing, and sex. Impact on genome stability BT - Abstracts of the 87th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) with contribution of the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e. V. (AGAH) T2 - Naunyn-Schmiedeberg's archives of pharmacology Y1 - 2021 U6 - https://doi.org/10.1007/s00210-021-02066-6 SN - 0028-1298 SN - 1432-1912 VL - 394 IS - Suppl. 1 SP - S13 EP - S13 PB - Springer CY - Berlin ; Heidelberg ER - TY - THES A1 - Koelman, Liselot A. T1 - The role of diet in immune health and ageing BT - integrating intervention and observational evidence Y1 - 2023 ER - TY - THES A1 - Haß, Ulrike T1 - Vergleich anti-inflammatorischer Ernährungsstrategien auf Inflammation und Muskelfunktion bei älteren Erwachsenen T1 - Comparison of anti-inflammatory dietary approaches on inflammation and muscle function in old adults N2 - Mit dem Alter kann eine Zunahme leichtgradiger Entzündungsprozesse beobachtet werden, von denen angenommen wird, dass sie den typischen, altersbedingten Verlust an Muskelmasse, -kraft und -funktion „befeuern“. Diese als Inflammaging bezeichneten Prozesse können auf ein komplexes Zusammenspiel aus einem dysfunktionalen (viszeralen) Fettgewebe, einer Dysbiose und damit einhergehender mikrobiellen Translokation und geringeren Abwehrfähigkeit sowie einer insgesamt zunehmenden Immunseneszenz zurückgeführt werden. In Summa begünstigt ein pro-inflammatorisches Milieu metabolische Störungen und chronische, altersassoziierte Erkrankungen, die das Entzündungsgeschehen aufrechterhalten oder vorantreiben. Neben einem essenziellen Bewegungsmangel trägt auch eine westlich geprägte, industrialisierte Ernährungsweise zum Entzündungsgeschehen und zur Entwicklung chronischer Erkrankungen bei. Daher liegt die Vermutung nahe, dem Entzündungsgeschehen mit ausreichend Bewegung und einer anti-inflammatorischen Ernährung entgegenzuwirken. In dieser Hinsicht werden insbesondere Omega-3-Fettsäuren (Omega-3) mit anti-inflammatorischen Eigenschaften verbunden. Obwohl ein Zusammenhang zwischen dem ernährungsbedingten Inflammationspotenzial bzw. der Zufuhr von Omega-3 und dem Inflammationsprofil bereits untersucht wurde, fehlen bislang Untersuchungen insbesondere bei älteren Erwachsenen, die den Link zwischen dem Inflammationspotenzial der Ernährung und Sarkopenie-relevanten Muskelparametern herstellen. Aufgrund des Proteinmehrbedarfs zum Erhalt der funktionellen Muskulatur im Alter wurde bereits eine Vielzahl an Sport- und Ernährungsinterventionen durchgeführt, die eine Verbesserung des Muskelstatus mit Hilfe von strukturiertem Krafttraining und einer proteinreichen Ernährung zeigen. Es gibt zudem Hinweise, dass Omega-3 auch die Proteinsynthese verstärken könnten. Unklar ist jedoch, inwiefern eine anti-inflammatorische Ernährung mit Fokus auf Omega-3 sowohl die Entzündungsprozesse als auch den Muskelproteinmetabolismus und die neuromuskuläre Funktionalität im Alter günstig unterstützen kann. Dies vor allem im Hinblick auf die Muskelleistung, die eng mit der Sturzneigung und der Autonomie im Alltag verknüpft ist, aber in Interventionsstudien mit älteren Erwachsenen bisher wenig Berücksichtigung erhielt. Darüber hinaus werden häufig progressive Trainingselemente genutzt, die nach Studienabschluss oftmals wenig Anschluss im Lebensalltag der Betroffenen finden und somit wenig nachhaltig sind. Ziel dieser Arbeit war demnach die Evaluierung einer proteinreichen und zusätzlich mit Omega-3 supplementierten Ernährung in Kombination mit einem wöchentlichen Vibrationstraining und altersgemäßen Bewegungsprogramm auf Inflammation und neuromuskuläre Funktion bei älteren, selbständig lebenden Erwachsenen. Hierzu wurden zunächst mögliche Zusammenhänge zwischen dem ernährungsbedingten Inflammationspotenzial, ermittelt anhand des Dietary Inflammatory Index, und dem Muskelstatus sowie dem Inflammationsprofil im Alter eruiert. Dazu dienten die Ausgangswerte von älteren, selbständig lebenden Erwachsenen einer postprandialen Interventionsstudie (POST-Studie), die im Querschnitt analysiert wurden. Die Ergebnisse bestätigten, dass eine pro-inflammatorische Ernährung sich einerseits in einem stärkeren Entzündungsgeschehen widerspiegelt und andererseits mit Sarkopenie-relevanten Parametern, wie einer geringeren Muskelmasse und Gehgeschwindigkeit, ungünstig assoziiert ist. Darüber hinaus zeigten sich diese Zusammenhänge auch in Bezug auf die Handgreifkraft bei den inaktiven, älteren Erwachsenen der Studie. Anschließend wurde in einer explorativ ausgerichteten Pilot-Interventionsstudie (AIDA-Studie) in einem dreiarmigen Design untersucht, inwieweit sich eine Supplementierung mit Omega-3 unter Voraussetzung einer optimierten Proteinzufuhr und altersgemäßen Sportintervention mit Vibrationstraining auf die neuromuskuläre Funktion und Inflammation bei selbständig lebenden, älteren Erwachsenen auswirkt. Nach acht Wochen Intervention zeigte sich, dass eine mit Omega-3 supplementierte, proteinreiche Ernährung die Muskelleistung insbesondere bei den älteren Männern steigerte. Während sich die Kontrollgruppe nach acht Wochen Sportintervention nicht verbesserte, bestätigte sich zusätzlich eine Verbesserung der Beinkraft und der Testzeit beim Stuhl-Aufsteh-Test der älteren Erwachsenen mit einer proteinreichen Ernährung in Kombination mit der Sportintervention. Darüber hinaus wurde deutlich, dass die zusätzliche Omega-3-Supplementierung insbesondere bei den Männern eine Reduktion der pro-inflammatorischen Zytokine im Serum zur Folge hatte. Allerdings spiegelten sich diese Beobachtungen nicht auf Genexpressionsebene in mononukleären Immunzellen oder in der LPS-induzierten Sekretion der Zytokine und Chemokine in Vollblutzellkulturen wider. Dies erfordert weitere Untersuchungen. N2 - With aging, a persistent low-grade inflammatory process can be observed, which is thought to "fuel" the typical age-related loss of muscle mass, strength and function. These processes, also known as inflammaging, can be attributed to a complex interplay of dysfunctional (visceral) adipose tissue, dysbiosis and associated microbial translocation, with a reduced immune defence and overall increasing immunosenescence. This pro-inflammatory milieu favours metabolic disorders and chronic, age-associated diseases, which in turn maintain or increase the inflammatory process. Additionally, inactivity and a westernized diet contribute to inflammation and the development of chronic diseases. Therefore, it is assumed that regular exercise and an anti-inflammatory diet can counteract inflammaging. In particular, omega-3 fatty acids (omega-3) are known for their anti-inflammatory properties. Although it has been shown that the dietary inflammatory load as well as the intake of omega-3 is associated with inflammation, studies that establish the link between the diet-related inflammatory load and sarcopenia-relevant muscle parameters are still lacking, especially in older adults. Due to the higher protein requirement to maintain muscle function in higher age, exercise and nutritional interventions have been extensively studied and consistently show improvements in muscle status with resistance exercise and high-protein diets. Experimental investigations indicate that omega-3 may also support protein synthesis. However, it is unclear to what extent an anti-inflammatory diet with focus on omega-3 can support the inflammatory processes as well as muscle protein metabolism and neuromuscular function in higher age. In particular muscle power, which is a key element of functionality and strongly related with fall risk, received little attention in interventional studies with older adults so far. In addition, exercise studies often use elements of progressive resistance training protocols, which, however, are seldom sustained by the participants in everyday life after intervention. Therefore, the aim of this work was to evaluate a high-protein diet supplemented with omega-3 in combination with an age-appropriate, home-based resistance exercise program and weekly vibration training on inflammation and neuromuscular function in community-dwelling older adults. For this purpose, cross-sectional associations between the diet-related inflammatory load, as determined by the Dietary Inflammatory Index, and muscle status as well as inflammation were investigated by baseline values of community-dwelling older adults, who participated in a postprandial intervention study (POST study). This cross-sectional analysis confirmed that a pro-inflammatory diet was reflected in a higher systemic inflammation and at the same time was associated with unfavourable sarcopenia-relevant parameters such as lower muscle mass and slower gait speed. In addition, a higher dietary inflammatory load and higher inflammation were both found to be associated with lower hand grip strength in inactive, older adults. Subsequently, the effects of an omega-3 supplemented, high-protein diet in combination with age-appropriate resistance exercises and weekly vibration training on neuromuscular function and inflammation were examined in community-dwelling older adults. For this purpose, an 8-week exploratory pilot trial in a three-arm study design (AIDA study) was carried out. It was shown that a high-protein diet, additionally supplemented with omega-3 increased muscle power particularly in older men. While the control group did not improve after eight weeks of exercise intervention, there was an improvement in leg strength and chair rise time in older adults receiving a high-protein diet combined with the exercise intervention. Moreover, an additional omega-3 supplementation resulted in a reduction of circulating pro-inflammatory cytokines in particular in older men. However, these observations in serum were not reflected on gene expression levels in mononuclear immune cells or in lipopolysaccharide-induced secretion of the cytokines and chemokines in whole blood cultures and requires further investigation. KW - Ernährung KW - nutrition KW - Gerontologie KW - gerontology KW - Sport KW - exercise KW - Muskelschwund KW - sarcopenia KW - Hoch-Protein Diät KW - high protein diet KW - Omega-3 Fettsäuren KW - omega-3 fatty acid Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-611976 ER - TY - THES A1 - Wittek, Laura T1 - Comparison of metabolic cages - analysis of refinement measures on the welfare and metabolic parameters of laboratory mice T1 - Der Vergleich von Stoffwechselkäfigen - Analyse von Refinement-Maßnahmen auf das Wohlbefinden und Stoffwechselparameter von Labormäusen N2 - Housing in metabolic cages can induce a pronounced stress response. Metabolic cage systems imply housing mice on metal wire mesh for the collection of urine and feces in addition to monitoring food and water intake. Moreover, mice are single-housed, and no nesting, bedding, or enrichment material is provided, which is often argued to have a not negligible impact on animal welfare due to cold stress. We therefore attempted to reduce stress during metabolic cage housing for mice by comparing an innovative metabolic cage (IMC) with a commercially available metabolic cage from Tecniplast GmbH (TMC) and a control cage. Substantial refinement measures were incorporated into the IMC cage design. In the frame of a multifactorial approach for severity assessment, parameters such as body weight, body composition, food intake, cage and body surface temperature (thermal imaging), mRNA expression of uncoupling protein 1 (Ucp1) in brown adipose tissue (BAT), fur score, and fecal corticosterone metabolites (CMs) were included. Female and male C57BL/6J mice were single-housed for 24 h in either conventional Macrolon cages (control), IMC, or TMC for two sessions. Body weight decreased less in the IMC (females—1st restraint: 6.94%; 2nd restraint: 6.89%; males—1st restraint: 8.08%; 2nd restraint: 5.82%) compared to the TMC (females—1st restraint: 13.2%; 2nd restraint: 15.0%; males—1st restraint: 13.1%; 2nd restraint: 14.9%) and the IMC possessed a higher cage temperature (females—1st restraint: 23.7°C; 2nd restraint: 23.5 °C; males—1st restraint: 23.3 °C; 2nd restraint: 23.5 °C) compared with the TMC (females—1st restraint: 22.4 °C; 2nd restraint: 22.5 °C; males—1st restraint: 22.6 °C; 2nd restraint: 22.4 °C). The concentration of fecal corticosterone metabolites in the TMC (females—1st restraint: 1376 ng/g dry weight (DW); 2nd restraint: 2098 ng/g DW; males—1st restraint: 1030 ng/g DW; 2nd restraint: 1163 ng/g DW) was higher compared to control cage housing (females—1st restraint: 640 ng/g DW; 2nd restraint: 941 ng/g DW; males—1st restraint: 504 ng/g DW; 2nd restraint: 537 ng/g DW). Our results show the stress potential induced by metabolic cage restraint that is markedly influenced by the lower housing temperature. The IMC represents a first attempt to target cold stress reduction during metabolic cage application thereby producing more animal welfare friendly data. N2 - Die Unterbringung in Stoffwechselkäfigen kann eine ausgeprägte Stressreaktion hervorrufen. Mäuse werden in Stoffwechselkäfigen auf Metallgittern gehalten, um zusätzlich zur Überwachung der Futter- und Wasseraufnahme Urin und Kot aufzufangen. Darüber hinaus werden die Mäuse einzeln gehalten und es wird kein Nist-, Einstreu- oder Anreicherungs-Material zur Verfügung gestellt, was oft als Ursache für Kältestress angeführt wird, welcher sich auf das Wohlergehen der Tiere auswirkt. Wir haben daher versucht, den Stress bei der Haltung von Mäusen in Stoffwechselkäfigen zu reduzieren, indem wir einen innovativen Stoffwechselkäfig (IMC) mit einem kommerziell erhältlichen Stoffwechselkäfig der Tecniplast GmbH (TMC) und einem Kontrollkäfig verglichen haben. Für das Käfigdesign des IMC wurden wesentliche Refinement-Maßnahmen realisiert. Im Rahmen einer multifaktoriellen Beurteilung des Schweregrades wurden Parameter wie Körpergewicht, Körperzusammensetzung, Nahrungsaufnahme, Käfig- und Körperoberflächentemperatur (Wärmebildaufnahmen), mRNA-Expression von Uncoupling Protein 1 (Ucp1) im braunen Fettgewebe (BAT), Fur Score und fäkale Corticosteron-Metabolite (CMs) einbezogen. Weibliche und männliche C57BL/6J-Mäuse wurden für jeweils 24 Stunden entweder in konventionellen Macrolon-Käfigen (Kontrolle), IMC oder TMC zweimal untergebracht. Das Körpergewicht nahm in dem IMC weniger ab (Weibchen - 1. Haltung: -6,94%; 2. Haltung: -6,89%; Männchen - 1. Haltung: -8,08%; 2. Haltung: -5,82%) als in dem TMC (Weibchen - 1. Haltung: -13,2%; 2. Haltung: -15,0%; Männchen - 1. Haltung: -13,1%; 2. Haltung: -14,9%) und der IMC wies eine höhere Käfigtemperatur (Weibchen - 1. Haltung: 23,7 °C; 2. Haltung 23,5 °C; Männchen - 1. Haltung: 23,3 °C; 2. Haltung: 23,5 °C) im Vergleich zum TMC auf (Weibchen - 1. Haltung: 22,4 °C; 2. Haltung: 22,5 °C; Männchen - 1. Haltung: 22,6 °C; 2. Haltung: 22,4 °C). Die Konzentration der fäkalen Corticosteron-Metabolite im TMC (Weibchen - 1. Haltung: 1376 ng/g Trockengewicht (DW); 2. Haltung: 2098 ng/g DW; Männchen – 1. Haltung: 1030 ng/g DW; 2. Haltung: 1163 ng/g DW) war im Vergleich zur Kontrollkäfighaltung höher (Weibchen - 1. Haltung: 640 ng/g DW; 2. Haltung: 941 ng/g DW; Männchen - 1. Haltung: 504 ng/g DW; 2. Haltung: 537 ng/g DW). Unsere Ergebnisse zeigen das Stresspotenzial, welches durch die Haltung in Stoffwechselkäfigen ausgelöst wird, und dass durch die niedrigere Haltungstemperatur deutlich beeinflusst wird. Der IMC stellt einen ersten Versuch dar, den Kältestress während der Anwendung des Stoffwechselkäfigs zu reduzieren und dadurch tierschutzgerechtere Daten zu produzieren. KW - metabolic cage KW - laboratory mice KW - refinement KW - animal welfare KW - Tierschutz KW - Labormäuse KW - Stoffwechselkäfig KW - Refinement Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-611208 ER - TY - JOUR A1 - Hackethal, Christin A1 - Kopp, Johannes Florian A1 - Sarvan, Irmela A1 - Schwerdtle, Tanja A1 - Lindtner, Oliver T1 - Total arsenic and water-soluble arsenic species in foods of the first German total diet study (BfR MEAL Study) JF - Food chemistry N2 - Arsenic can occur in foods as inorganic and organic forms. Inorganic arsenic is more toxic than most watersoluble organic arsenic compounds such as arsenobetaine, which is presumed to be harmless for humans. Within the first German total diet study, total arsenic, inorganic arsenic, arsenobetaine, dimethylarsinic acid and monomethylarsonic acid were analyzed in various foods. Highest levels of total arsenic were found in fish, fish products and seafood (mean: 1.43 mg kg(-1); n = 39; min-max: 0.01-6.15 mg kg(-1)), with arsenobetaine confirmed as the predominant arsenic species (1.233 mg kg 1; n = 39; min-max: 0.01-6.23 mg kg (1)). In contrast, inorganic arsenic was determined as prevalent arsenic species in terrestrial foods (0.02 mg kg (1); n = 38; min-max: 0-0.11 mg kg (1)). However, the toxicity of arsenic species varies and measurements are necessary to gain information about the composition and changes of arsenic species in foods due to household processing of foods. KW - Occurrence data KW - Food KW - Total arsenic KW - Arsenic speciation KW - Inductively KW - coupled plasma mass spectrometry Y1 - 2021 U6 - https://doi.org/10.1016/j.foodchem.2020.128913 SN - 0308-8146 SN - 1873-7072 VL - 346 PB - Elsevier CY - Amsterdam [u.a.] ER - TY - JOUR A1 - Raupbach, Jana A1 - Ott, Christiane A1 - König, Jeannette A1 - Grune, Tilman T1 - Proteasomal degradation of glycated proteins depends on substrate unfolding: Preferred degradation of moderately modified myoglobin JF - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research N2 - The Maillard reaction generates protein modifications which can accumulate during hyperglycemia or aging and may have inflammatory consequences. The proteasome is one of the major intracellular systems involved in the proteolytic degradation of modified proteins but its role in the degradation of glycated proteins is scarcely studied. In this study, chemical and structural changes of glycated myoglobin were analyzed and its degradation by 20S proteasome was studied. Myoglobin was incubated with physiological (5-10 mM), moderate (50-100 mM) and severe levels (300 mM) of glucose or methylglyoxal (MGO, 50 mM). Glycation increased myoglobin's fluorescence and surface hydrophobicity. Severe glycation generated crosslinked proteins as shown by gel electrophoresis. The concentration of advanced glycation endproducts (AGEs) N-epsilon-carboxymethyl lysine (CML), N-epsilon-carboxyethyl lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), pentosidine and pyrraline was analyzed after enzymatic hydrolysis followed by UPLC-MS/MS. Higher concentrations of glucose increased all analyzed AGEs and incubation with MGO led to a pronounced increase of CEL and MG-H1. The binding of the heme group to apo-myoglobin was decreased with increasing glycation indicating the loss of tertiary protein structure. Proteasomal degradation of modified myoglobin compared to native myoglobin depends on the degree of glycation: physiological conditions decreased proteasomal degradation whereas moderate glycation increased degradation. Severe glycation again decreased proteolytic cleavage which might be due to crosslinking of protein monomers. The activity of the proteasomal subunit beta 5 is influenced by the presence of glycated myoglobin. In conclusion, the role of the proteasome in the degradation of glycated proteins is highly dependent on the level of glycation and consequent protein unfolding. KW - Glycation KW - Myoglobin KW - Heme KW - Advanced glycation endproducts KW - 20S KW - proteasome Y1 - 2020 U6 - https://doi.org/10.1016/j.freeradbiomed.2019.11.024 SN - 0891-5849 SN - 1873-4596 VL - 152 SP - 516 EP - 524 PB - Elsevier CY - New York ER - TY - JOUR A1 - Gohlke, Sabrina A1 - Mancini, Carola A1 - Garcia-Carrizo, Francisco A1 - Schulz, Tim J. T1 - Loss of the ciliary gene Bbs4 results in defective thermogenesis due to metabolic inefficiency and impaired lipid metabolism JF - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology N2 - Adipose tissue is central to the regulation of energy balance. While white adipose tissue (WAT) is responsible for triglyceride storage, brown adipose tissue specializes in energy expenditure. Deterioration of brown adipocyte function contributes to the development of metabolic complications like obesity and diabetes. These disorders are also leading symptoms of the Bardet-Biedl syndrome (BBS), a hereditary disorder in humans which is caused by dysfunctions of the primary cilium and which therefore belongs to the group of ciliopathies. The cilium is a hair-like organelle involved in cellular signal transduction. The BBSome, a supercomplex of several Bbs gene products, localizes to the basal body of cilia and is thought to be involved in protein sorting to and from the ciliary membrane. The effects of a functional BBSome on energy metabolism and lipid mobilization in brown and white adipocytes were tested in whole-body Bbs4 knockout mice that were subjected to metabolic challenges. Chronic cold exposure reveals cold-intolerance of knockout mice but also ameliorates the markers of metabolic pathology detected in knockouts prior to cold. Hepatic triglyceride content is markedly reduced in knockout mice while circulating lipids are elevated, altogether suggesting that defective lipid metabolism in adipose tissue creates increased demand for systemic lipid mobilization to meet energetic demands of reduced body temperatures. These findings taken together suggest that Bbs4 is essential for the regulation of adipose tissue lipid metabolism, representing a potential target to treat metabolic disorders. KW - adipose tissue KW - Bbs4 KW - BBsome KW - browning KW - cilium KW - lipid metabolism Y1 - 2021 U6 - https://doi.org/10.1096/fj.202100772RR SN - 1530-6860 VL - 35 IS - 11 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Häseli, Steffen A1 - Deubel, Stefanie A1 - Jung, Tobias A1 - Grune, Tilman A1 - Ott, Christiane T1 - Cardiomyocyte contractility and autophagy in a premature senescence model of cardiac aging JF - Oxidative medicine and cellular longevity N2 - Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated beta-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy. Y1 - 2020 U6 - https://doi.org/10.1155/2020/8141307 SN - 1942-0994 VL - 2020 IS - Special Issue PB - Landes Bioscience CY - Austin, Tex. ER - TY - JOUR A1 - Ost, Mario A1 - Igual Gil, Carla A1 - Coleman, Verena A1 - Keipert, Susanne A1 - Efstathiou, Sotirios A1 - Vidic, Veronika A1 - Weyers, Miriam A1 - Klaus, Susanne T1 - Muscle-derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress JF - EMBO reports N2 - Mitochondrial dysfunction promotes metabolic stress responses in a cell-autonomous as well as organismal manner. The wasting hormone growth differentiation factor 15 (GDF15) is recognized as a biomarker of mitochondrial disorders, but its pathophysiological function remains elusive. To test the hypothesis that GDF15 is fundamental to the metabolic stress response during mitochondrial dysfunction, we investigated transgenic mice (Ucp1-TG) with compromised muscle-specific mitochondrial OXPHOS capacity via respiratory uncoupling. Ucp1-TG mice show a skeletal muscle-specific induction and diurnal variation of GDF15 as a myokine. Remarkably, genetic loss of GDF15 in Ucp1-TG mice does not affect muscle wasting or transcriptional cell-autonomous stress response but promotes a progressive increase in body fat mass. Furthermore, muscle mitochondrial stress-induced systemic metabolic flexibility, insulin sensitivity, and white adipose tissue browning are fully abolished in the absence of GDF15. Mechanistically, we uncovered a GDF15-dependent daytime-restricted anorexia, whereas GDF15 is unable to suppress food intake at night. Altogether, our evidence suggests a novel diurnal action and key pathophysiological role of mitochondrial stress-induced GDF15 in the regulation of systemic energy metabolism. KW - anorexia KW - GDF15 KW - integrated stress response KW - mitochondrial dysfunction KW - muscle wasting Y1 - 2020 U6 - https://doi.org/10.15252/embr.201948804 SN - 1469-221X SN - 1469-3178 VL - 21 IS - 3 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Kehm, Richard A1 - Jähnert, Markus A1 - Deubel, Stefanie A1 - Flore, Tanina A1 - König, Jeannette A1 - Jung, Tobias A1 - Stadion, Mandy A1 - Jonas, Wenke A1 - Schürmann, Annette A1 - Grune, Tilman A1 - Höhn, Annika T1 - Redox homeostasis and cell cycle activation mediate beta-cell mass expansion in aged, diabetes-prone mice under metabolic stress conditions: role of thioredoxin-interacting protein (TXNIP) JF - Redox Biology N2 - Overnutrition contributes to insulin resistance, obesity and metabolic stress, initiating a loss of functional beta-cells and diabetes development. Whether these damaging effects are amplified in advanced age is barely investigated. Therefore, New Zealand Obese (NZO) mice, a well-established model for the investigation of human obesity-associated type 2 diabetes, were fed a metabolically challenging diet with a high-fat, carbohydrate restricted period followed by a carbohydrate intervention in young as well as advanced age. Interestingly, while young NZO mice developed massive hyperglycemia in response to carbohydrate feeding, leading to beta-cell dysfunction and cell death, aged counterparts compensated the increased insulin demand by persistent beta-cell function and beta-cell mass expansion. Beta-cell loss in young NZO islets was linked to increased expression of thioredoxin-interacting protein (TXNIP), presumably initiating an apoptosis-signaling cascade via caspase-3 activation. In contrast, islets of aged NZOs exhibited a sustained redox balance without changes in TXNIP expression, associated with higher proliferative potential by cell cycle activation. These findings support the relevance of a maintained proliferative potential and redox homeostasis for preserving islet functionality under metabolic stress, with the peculiarity that this adaptive response emerged with advanced age in diabetesprone NZO mice. KW - aging KW - redox homeostasis KW - metabolic stress KW - beta-cells KW - cell cycle KW - thioredoxin-interacting protein Y1 - 2020 U6 - https://doi.org/10.1016/j.redox.2020.101748 SN - 2213-2317 VL - 37 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Nicolai, Merle Marie A1 - Baesler, Jessica A1 - Aschner, Michael A1 - Schwerdtle, Tanja A1 - Bornhorst, Julia T1 - Consequences of manganese overload in C. elegans BT - oxidative stress and DNA damage JF - Naunyn-Schmiedeberg's archives of pharmacology / ed. for the Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie Y1 - 2020 U6 - https://doi.org/10.1007/s00210-020-01828-y SN - 0028-1298 SN - 1432-1912 VL - 393 IS - SUPPL 1 SP - 9 EP - 9 PB - Springer CY - New York ER - TY - JOUR A1 - Borremans, An A1 - Bußler, Sara A1 - Sagu Tchewonpi, Sorel A1 - Rawel, Harshadrai Manilal A1 - Schlüter, Oliver K. A1 - Leen, Van Campenhout T1 - Effect of blanching plus fermentation on selected functional properties of mealworm (Tenebrio molitor) powders JF - Foods : open access journal N2 - The aim of this study was to determine the effect of blanching followed by fermentation of mealworms (Tenebrio molitor) with commercial meat starter cultures on the functional properties of powders produced from the larvae. Full fat and defatted powder samples were prepared from non-fermented and fermented mealworm pastes. Then the crude protein, crude fat, and dry matter contents, pH, bulk density, colour, water and oil binding capacity, foaming capacity and stability, emulsion capacity and stability, protein solubility, quantity of free amino groups, and protein composition of the powders were evaluated. Regardless of the starter culture used, the blanching plus fermentation process reduced the crude and soluble protein contents of the full fat powders and in general impaired their water and oil binding, foaming, and emulsifying properties. Defatting of the powders improved most functional properties studied. The o-phthaldialdehyde assay revealed that the amount of free amino groups was higher in the fermented powders while sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the soluble proteins of the fermented powders were composed of molecules of lower molecular mass compared to non-fermented powders. As molecular sizes of the soluble proteins decreased, it was clear that the protein structure was also modified by the fermentation process, which in turn led to changes in functional properties. In general, it was concluded that fermentation of mealworms with blanching as a pre-treatment does not contribute to the functional properties studied in this work. Nevertheless, the results confirmed that the properties of non-fermented powders are comparable to other food protein sources. KW - mealworm KW - fermentation KW - functional properties KW - insect proteins KW - SDS-PAGE Y1 - 2020 U6 - https://doi.org/10.3390/foods9070917 SN - 2304-8158 VL - 9 IS - 7 PB - MDPI CY - Basel ER - TY - JOUR A1 - Stadion, Mandy A1 - Schürmann, Annette T1 - Intermittierendes Fasten BT - was gibt es Neues aus der Wissenschaft? BT - what’s new from science? JF - Der Diabetologe N2 - Obesity increases the risk of metabolic disorders and can lead to type 2 diabetes. Therefore, the treatment and prevention of obesity represent important medical challenges. Increased physical activity and a reduction in daily caloric intake of 25-30% are often recommended. Another possibility is intermittent fasting, by limiting dietary caloric content over certain times, i.e. one or more days a week or for more than 14 h a day. Animal and human studies provide evidence that intermittent fasting in obesity leads to a reduction in body fat mass as well as to improvements of metabolic parameters and insulin sensitivity. These positive effects are mediated not only by the decrease in body mass, but also by the activation of metabolic pathways and cellular processes that are specific for fasting conditions. In this article, we describe the current knowledge about the mechanisms induced by intermittent fasting and present results from randomized controlled human trials. N2 - Übergewicht und Adipositas erhöhen die Risiken für Stoffwechselstörungen und können zu einem Typ-2-Diabetes führen. Deshalb stellen die Behandlung und Prävention von Fettleibigkeit eine große medizinische Herausforderung dar. Häufig werden eine erhöhte körperliche Aktivität und die Reduktion der täglichen Kalorienaufnahme um 25–30 % angeraten. Eine andere Möglichkeit bietet intermittierendes Fasten, also eine Kalorieneinschränkung über bestimmte Zeiten, d. h. an einem oder mehreren Tagen pro Woche oder über mehr als 14 h pro Tag. Tier- und Humanstudien lieferten Hinweise darauf, dass intermittierendes Fasten bei Adipositas zu einer Verringerung der Körperfettmasse sowie zu Verbesserungen der Stoffwechselparameter und der Insulinsensitivität führt. Diese positiven Effekte werden nicht nur allein durch die Abnahme der Körpermasse, sondern auch durch die Aktivierung von Stoffwechselwegen und zellulären Prozessen ausgelöst, die für Fastenbedingungen spezifisch sind. In diesem Artikel beschreiben wir die derzeit bekannten Mechanismen, die durch intermittierendes Fasten induziert werden, und stellen Ergebnisse aus randomisierten kontrollierten Studien am Menschen vor. T2 - Intermittent fasting KW - Glucose metabolism disorders KW - Lipid metabolism KW - Insulin sensitivity KW - Energy metabolism KW - Circadian rhythm KW - Glukosestoffwechselstörungen KW - Fettstoffwechsel KW - Insulinsensitivität KW - Energiestoffwechsel KW - Zirkadianer Rhythmus Y1 - 2020 U6 - https://doi.org/10.1007/s11428-020-00666-z SN - 1860-9716 SN - 1860-9724 VL - 16 IS - 7 SP - 641 EP - 646 PB - Springer Medizin CY - Berlin ER - TY - JOUR A1 - Grune, Tilman T1 - Oxidized protein aggregates BT - formation and biological effects JF - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research N2 - The study of protein aggregates has a long history. While in the first decades until the 80ies of the 20th century only the observation of the presence of such aggregates was reported, later the biochemistry of the formation and the biological effects of theses aggregates were described. This review focusses on the complexity of the biological effects of protein aggregates and its potential role in the aging process. Y1 - 2020 U6 - https://doi.org/10.1016/j.freeradbiomed.2020.02.014 SN - 0891-5849 SN - 1873-4596 VL - 150 SP - 120 EP - 124 PB - Elsevier CY - New York ER - TY - JOUR A1 - Wright, Stephanie L. A1 - Ulke, Jannis A1 - Font, Anna A1 - Chan, Ka Lung Andrew A1 - Kelly, Frank J. T1 - Atmospheric microplastic deposition in an urban environment and an evaluation of transport JF - Environment international N2 - Microplastics are a global environmental issue contaminating aquatic and terrestrial environments. They have been reported in atmospheric deposition, and indoor and outdoor air, raising concern for public health due to the potential for exposure. Moreover, the atmosphere presents a new vehicle for microplastics to enter the wider environment, yet our knowledge of the quantities, characteristics and pathways of airborne microplastics is sparse. Here we show microplastics in atmospheric deposition in a major population centre, central London. Microplastics were found in all samples, with deposition rates ranging from 575 to 1008 microplastics/m(2)/d. They were found in various shapes, of which fibrous microplastics accounted for the great majority (92%). Across all samples, 15 different petrochemical-based polymers were identified. Bivariate polar plots indicated dependency on wind, with different source areas for fibrous and non-fibrous airborne microplastics. This is the first evidence of airborne microplastics in London and confirms the need to include airborne pathways when consolidating microplastic impacts on the wider environment and human health. KW - microplastics KW - atmospheric deposition KW - air pollution KW - urban Y1 - 2020 U6 - https://doi.org/10.1016/j.envint.2019.105411 SN - 0160-4120 SN - 1873-6750 VL - 136 PB - Elsevier, Pergamon Press CY - New York, NY [u.a.] ER - TY - THES A1 - Lopes Fernando, Raquel Sofia T1 - The impact of aging on proteolytic systems, transcriptome and metabolome of slow and fast muscle fiber types N2 - Aging is a complex process characterized by several factors, including loss of genetic and epigenetic information, accumulation of chronic oxidative stress, protein damage and aggregates and it is becoming an emergent drug target. Therefore, it is the utmost importance to study aging and agerelated diseases, to provide treatments to develop a healthy aging process. Skeletal muscle is one of the earliest tissues affected by age-related changes with progressive loss of muscle mass and function from 30 years old, effect known as sarcopenia. Several studies have shown the accumulation of protein aggregates in different animal models, as well as in humans, suggesting impaired proteostasis, a hallmark of aging, especially regarding degradation systems. Thus, different publications have explored the role of the main proteolytic systems in skeletal muscle from rodents and humans, like ubiquitin proteasomal system (UPS) and autophagy lysosomal system (ALS), however with contradictory results. Yet, most of the published studies are performed in muscles that comprise more than one fiber type, that means, muscles composed by slow and fast fibers. These fiber types, exhibit different metabolism and contraction speed; the slow fibers or type I display an oxidative metabolism, while fast fibers function towards a glycolytic metabolism ranging from fast oxidative to fast glycolytic fibers. To this extent, the aim of this thesis sought to understand on how aging impacts both fiber types not only regarding proteostasis but also at a metabolome and transcriptome network levels. Therefore, the first part of this thesis, presents the differences between slow oxidative (from Soleus muscle) and fast glycolytic fibers (Extensor digitorum longus, EDL) in terms of degradation systems and how they cope with oxidative stress during aging, while the second part explores the differences between young and old EDL muscle transcriptome and metabolome, unraveling molecular features. More specifically, the results from the present work show that slow oxidative muscle performs better at maintaining the function of UPS and ALS during aging than EDL muscle, which is clearly affected, accounting for the decline in the catalytic activity rates and accumulation of autophagy-related proteins. Strinkingly, transcriptome and metabolome analyses reveal that fast glycolytic muscle evidences significant downregulation of mitochondrial related processes and damaged mitochondria morphology during aging, despite of having a lower oxidative metabolism compared to oxidative fibers. Moreover, predictive analyses reveal a negative association between aged EDL gene signature and lifespan extending interventions such as caloric restriction (CR). Although, CR intervention does not alter the levels of mitochondrial markers in aged EDL muscle, it can reverse the higher mRNA levels of muscle damage markers. Together, the results from this thesis give new insights about how different metabolic muscle fibers cope with age-related changes and why fast glycolytic fibers are more susceptible to aging than slow oxidative fibers. N2 - Altern ist ein komplexer Prozess, der durch mehrere Faktoren gekennzeichnet ist, darunter der Verlust genetischer und epigenetischer Informationen, oxidativer Stress, sowie die Anhäufung von Proteinschäden und Aggregaten. Daher ist es von größter Bedeutung, das Altern und altersbedingte Krankheiten zu erforschen, um Arzneimittel und andere Behandlungen für einen gesunden Alterungsprozess zu entwickeln. Die Skelettmuskulatur ist eines der ersten Gewebe, das von altersbedingten Veränderungen betroffen ist. Ab einem Alter von 30 Jahren kommt es zu einem fortschreitenden Verlust der Muskelmasse und -funktion, der auch als Sarkopenie bezeichnet wird. Mehrere Studien haben die Anhäufung von Proteinaggregaten beim Altern in verschiedenen Tiermodellen und auch beim Menschen gezeigt, was auf eine gestörte Proteostase, insbesondere hinsichtlich der Abbauprozesse schließen lässt. Demnach wurde weiterführend die Rolle der wichtigsten proteolytischen Systeme, das Ubiquitin Proteasom System (UPS) und AutophagieLysosomale System (ALS), im alternden Skelettmuskel von Nagetieren und Menschen untersucht. Die Ergebnisse waren widersprüchlich, jedoch wurden die meisten der veröffentlichten Studien an Muskeln durchgeführt, die aus mehr als einem Muskelfasertyp bestehen, d.h. Muskeln, die aus langsamen und schnellen Muskelfasern zusammengesetzt sind. Diese Muskelfasertypen unterscheiden sich hinsichtlich des Stoffwechsels und der Kontraktionsgeschwindigkeit. Die langsamen Fasern oder der Typ I haben einen oxidativen Stoffwechsel, während die schnellen Fasern einen glykolytischen Stoffwechsel aufweisen und aus schnellen oxidativen bis zu schnellen glykolytischen Fasern bestehen können. Insofern war es das Ziel dieser Arbeit zu verstehen, wie sich das Altern auf beide Fasertypen auswirkt, und zwar nicht nur im Hinblick auf die Proteostase, sondern auch auf das Metabolom und Transkriptom. Im ersten Teil dieser Arbeit werden die Unterschiede zwischen langsamen oxidativen (Soleus-Muskel) und schnellen glykolytischen Fasern (Extensor digitorum longus-Muskel; EDL) in Bezug auf die Proteinabbausysteme und die Art und Weise, wie sie mit oxidativem Stress während des Alterns umgehen, dargestellt. Im zweiten Teil werden die Unterschiede zwischen dem Transkriptom und dem Metabolom des jungen und alten EDL-Muskels untersucht, um die molekularen Merkmale zu entschlüsseln. Im Einzelnen zeigen die Ergebnisse der vorliegenden Arbeit, dass der langsam oxidierende Muskel im Vergleich zum EDL-Muskel besser in der Lage ist, die Funktion von UPS und ALS während des Alterns aufrechtzuerhalten. Die Funktionalität des UPS und ALS ist im alternden EDL-Muskels vermindert, was durch den Rückgang der katalytischen Aktivitätsraten und die Anhäufung von mit Autophagie-assoziierten Proteinen gezeigt wurde. Transkriptom- und Metabolomanalysen zeigen, dass schnelle glykolytische Muskeln eine signifikante Herabregulierung mitochondrialer Prozesse und eine geschädigte Mitochondrienmorphologie während des Alterns aufweisen, obwohl sie im Vergleich zu oxidativen Fasern durch einen geringeren oxidativen Stoffwechsel charakterisiert sind. Darüber hinaus ergeben prädiktive Analysen einen negativen Zusammenhang zwischen der Gensignatur des gealterten EDL-Muskels und lebensverlängernden Maßnahmen wie der kalorischenRestriktion. Obwohl die kalorischen Restriktion Intervention die Werte der mitochondrialen Marker im gealterten EDL-Muskel nicht verändert, kann sie die höheren mRNA-Werte der Muskelschädigungsmarker umkehren. Zusammenfassend liefern die Ergebnisse dieser Arbeit neue Erkenntnisse darüber, wie verschiedene metabolische Muskelfasern mit altersbedingten. Veränderungen umgehen und warum schnelle glykolytische Fasern anfälliger für die Alterung als langsame oxidative Fasern sind. KW - skeletal muscle aging KW - proteostasis KW - slow and fast fiber types KW - transcriptomics KW - metabolomics KW - sarcopenia KW - Skelettmuskelalterung KW - Proteostase KW - langsame und schnelle Fasertypen KW - Transkriptom KW - Metabolom KW - ubiquitin proteasomal system KW - autophagy lysosomal system KW - Ubiquitin Proteasom System KW - Autophagie Lysosomale System Y1 - 2023 U6 - https://doi.org/10.25932/publishup-60579 ER - TY - JOUR A1 - Weitkunat, Karolin A1 - Bishop, Christopher Allen A1 - Wittmüss, Maria A1 - Machate, Tina A1 - Schifelbein, Tina A1 - Schulze, Matthias Bernd A1 - Klaus, Susanne T1 - Effect of microbial status on hepatic odd-chain fatty acids is diet-dependent JF - Nutrients / Molecular Diversity Preservation International (MDPI) N2 - Odd-chain fatty acids (OCFA) are inversely associated with type-2-diabetes in epidemiological studies. They are considered as a biomarker for dairy intake because fermentation in ruminants yields high amounts of propionate, which is used as the primer for lipogenesis. Recently, we demonstrated endogenous OCFA synthesis from propionate in humans and mice, but how this is affected by microbial colonization is still unexplored. Here, we investigated the effect of increasing microbiota complexity on hepatic lipid metabolism and OCFA levels in different dietary settings. Germ-free (GF), gnotobiotic (SIH, simplified human microbiota) or conventional (CONV) C3H/HeOuJ-mice were fed a CHOW or high-fat diet with inulin (HFI) to induce microbial fermentation. We found that hepatic lipogenesis was increased with increasing microbiota complexity, independently of diet. In contrast, OCFA formation was affected by diet as well as microbiota. On CHOW, hepatic OCFA and intestinal gluconeogenesis decreased with increasing microbiota complexity (GF > SIH > CONV), while cecal propionate showed a negative correlation with hepatic OCFA. On HFI, OCFA levels were highest in SIH and positively correlated with cecal propionate. The propionate content in the CHOW diet was 10 times higher than that of HFI. We conclude that bacterial propionate production affects hepatic OCFA formation, unless this effect is masked by dietary propionate intake. KW - pentadecanoic acid (C15:0) KW - heptadecanoic acid (C17:0) KW - type-2-diabetes KW - fatty acid synthesis KW - acetate KW - propionate KW - probiotics KW - gut microbiota KW - prebiotics KW - inulin Y1 - 2021 U6 - https://doi.org/10.3390/nu13051546 SN - 2072-6643 VL - 13 IS - 5 PB - MDPI CY - Basel ER - TY - THES A1 - Raschke, Stefanie T1 - Characterization of selenium and copper in cell systems of the neurovascular unit T1 - Charakterisierung von Selen und Kupfer in Zellsystemen der neurovaskulären Einheit N2 - The trace elements, selenium (Se) and copper (Cu) play an important role in maintaining normal brain function. Since they have essential functions as cofactors of enzymes or structural components of proteins, an optimal supply as well as a well-defined homeostatic regulation are crucial. Disturbances in trace element homeostasis affect the health status and contribute to the incidence and severity of various diseases. The brain in particular is vulnerable to oxidative stress due to its extensive oxygen consumption and high energy turnover, among other factors. As components of a number of antioxidant enzymes, both elements are involved in redox homeostasis. However, high concentrations are also associated with the occurrence of oxidative stress, which can induce cellular damage. Especially high Cu concentrations in some brain areas are associated with the development and progression of neurodegenerative diseases such as Alzheimer's disease (AD). In contrast, reduced Se levels were measured in brains of AD patients. The opposing behavior of Cu and Se renders the study of these two trace elements as well as the interactions between them being particularly relevant and addressed in this work. N2 - Die Spurenelemente Selen (Se) und Kupfer (Cu) spielen eine wichtige Rolle bei der Aufrechterhaltung einer normalen Ge¬hirnfunktion. Da sie wesentliche Funktionen als Cofaktoren von Enzymen oder Strukturbestandteile von Proteinen haben, sind eine optimale Versorgung sowie eine genau definierte homöostatische Regulierung von entscheidender Bedeutung. Störungen der Spurenelement-homöostase beeinträchtigen den Gesund¬heitszustand und tragen zum Auftreten und zur Schwere verschiedener Krankheiten bei. Insbesondere das Gehirn ist aufgrund seines hohen Sauerstoffverbrauchs und seines hohen Energieumsatzes anfällig für oxi¬dativen Stress. Als Bestandteile einer Reihe von antioxidativen Enzymen sind beide Elemente an der Redox-Homöostase beteiligt. Hohe Konzentrationen werden jedoch auch mit dem Auftreten von oxidati¬vem Stress in Verbindung gebracht, der zu Zellschäden führen kann. Besonders hohe Cu-Konzentrationen in einigen Hirnregionen werden mit der Entwicklung und der Progression neurodegenerativer Erkran¬kungen wie Alzheimer in Verbindung gebracht. Im Gegensatz dazu wurden in den Gehirnen von Alzheimer-Patienten geringere Se-Konzentrationen gemessen. Das gegensätzliche Verhalten von Cu und Se verdeutlicht die Relevanz der Untersuchung dieser beiden Spurenelemente sowie deren Wechselwirkungen und wird in dieser Arbeit thematisiert. KW - selenium KW - copper KW - Selen KW - Kupfer KW - Blut-Hirn-Schranke KW - Neuronen KW - Astrozyten KW - blood-brain barrier KW - neurons KW - astrocytes Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-603666 ER - TY - GEN A1 - Kotthoff, Lisa A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Prediction of transformation products of monensin by electrochemistry compared to microsomal assay and hydrolysis T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid+ chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1340 KW - transformation products KW - monensin KW - veterinary drugs KW - electrochemistry KW - hydrolysis KW - LC/HRMS Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-473262 SN - 1866-8372 IS - 1340 ER - TY - GEN A1 - Rancan, Fiorenza A1 - Volkmann, Hildburg A1 - Giulbudagian, Michael A1 - Schumacher, Fabian A1 - Stanko, Jessica Isolde A1 - Kleuser, Burkhard A1 - Blume-Peytavi, Ulrike A1 - Calderón, Marcelo A1 - Vogt, Annika T1 - Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1339 KW - tacrolimus formulation KW - nanogels KW - skin penetration KW - drug delivery KW - human excised skin KW - Jurkat cells Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-473270 SN - 1866-8372 IS - 1339 ER - TY - JOUR A1 - Wetzel, Alexandra Nicole A1 - Scholtka, Bettina A1 - Schumacher, Fabian A1 - Rawel, Harshadrai Manilal A1 - Geisendörfer, Birte A1 - Kleuser, Burkhard T1 - Epigenetic DNA methylation of EBI3 modulates human interleukin-35 formation via NFkB signaling BT - a promising therapeutic option in ulcerative colitis JF - International journal of molecular sciences N2 - Ulcerative colitis (UC), a severe chronic disease with unclear etiology that is associated with increased risk for colorectal cancer, is accompanied by dysregulation of cytokines. Epstein-Barr virus-induced gene 3 (EBI3) encodes a subunit in the unique heterodimeric IL-12 cytokine family of either pro- or anti-inflammatory function. After having recently demonstrated that upregulation of EBI3 by histone acetylation alleviates disease symptoms in a dextran sulfate sodium (DSS)-treated mouse model of chronic colitis, we now aimed to examine a possible further epigenetic regulation of EBI3 by DNA methylation under inflammatory conditions. Treatment with the DNA methyltransferase inhibitor (DNMTi) decitabine (DAC) and TNF alpha led to synergistic upregulation of EBI3 in human colon epithelial cells (HCEC). Use of different signaling pathway inhibitors indicated NF kappa B signaling was necessary and proportional to the synergistic EBI3 induction. MALDI-TOF/MS and HPLC-ESIMS/MS analysis of DAC/TNF alpha-treated HCEC identified IL-12p35 as the most probable binding partner to form a functional protein. EBI3/IL-12p35 heterodimers (IL-35) induce their own gene upregulation, something that was indeed observed in HCEC cultured with media from previously DAC/TNF alpha-treated HCEC. These results suggest that under inflammatory and demethylating conditions the upregulation of EBI3 results in the formation of anti-inflammatory IL-35, which might be considered as a therapeutic target in colitis. KW - decitabine KW - DNMT inhibitor KW - EBI3 KW - inhibitory cytokines KW - interleukin-35 KW - TNF alpha KW - Ulcerative colitis Y1 - 2021 U6 - https://doi.org/10.3390/ijms22105329 SN - 1422-0067 VL - 22 IS - 10 PB - MDPI CY - Basel ER - TY - JOUR A1 - Gehre, Christian A1 - Flechner, Marie A1 - Kammerer, Sarah A1 - Küpper, Jan-Heiner A1 - Coleman, Charles Dominic A1 - Püschel, Gerhard Paul A1 - Uhlig, Katja A1 - Duschl, Claus T1 - Real time monitoring of oxygen uptake of hepatocytes in a microreactor using optical microsensors JF - Scientific reports N2 - Most in vitro test systems for the assessment of toxicity are based on endpoint measurements and cannot contribute much to the establishment of mechanistic models, which are crucially important for further progress in this field. Hence, in recent years, much effort has been put into the development of methods that generate kinetic data. Real time measurements of the metabolic activity of cells based on the use of oxygen sensitive microsensor beads have been shown to provide access to the mode of action of compounds in hepatocytes. However, for fully exploiting this approach a detailed knowledge of the microenvironment of the cells is required. In this work, we investigate the cellular behaviour of three types of hepatocytes, HepG2 cells, HepG2-3A4 cells and primary mouse hepatocytes, towards their exposure to acetaminophen when the availability of oxygen for the cell is systematically varied. We show that the relative emergence of two modes of action, one NAPQI dependent and the other one transient and NAPQI independent, scale with expression level of CYP3A4. The transient cellular response associated to mitochondrial respiration is used to characterise the influence of the initial oxygen concentration in the wells before exposure to acetaminophen on the cell behaviour. A simple model is presented to describe the behaviour of the cells in this scenario. It demonstrates the level of control over the role of oxygen supply in these experiments. This is crucial for establishing this approach into a reliable and powerful method for the assessment of toxicity. Y1 - 2020 U6 - https://doi.org/10.1038/s41598-020-70785-6 SN - 2045-2322 VL - 10 IS - 1 PB - Macmillan Publishers Limited, part of Springer Nature CY - [London] ER - TY - JOUR A1 - Schiborn, Catarina A1 - Schulze, Matthias Bernd T1 - Diabetes risk scores T1 - Diabetesrisikoscores BT - use in diabetes prevention BT - Einsatz in der Diabetesprävention JF - Der Diabetologe N2 - Risk scores are used to identify high-risk individuals for type 2 diabetes (T2DM) who benefit from preventive measures. The DIfE-DEUTSCHER DIABETES-RISIKO-TEST (R) (DRT) is used to determine the absolute 5-year risk for T2DM. Since the calculation is based on non-clinical information, the test can be used independently of a doctor's visit. Data from prospective population-based long-term studies serve as the basis for the development of risk scores. As in the case of the DRT, the very good predictive quality of a score should be confirmed in independent populations. In addition to the use by doctors and for individual self-anamnesis, non-clinical risk scores can be used in the context of broader, population-based prevention concepts and information offers to reduce the risk of disease. Prevention services billable by health insurance companies should support the integration of health-promoting behavior into everyday life within the meaning of the German Prevention Act. Although obesity and diet are relevant lifestyle risk factors for T2DM, the proportion of preventive courses taken on this topic is only 3% of the courses billed. Appropriate recommendations in medical examinations could promote more extensive use. The use of risk scores as the basis for systematic and targeted recommendations for behavioral prevention could also support this, as is already established in guidelines for cardiovascular prevention. The further development of implementation research is also important for the efficient use of risk scores. N2 - Risikoscores werden zur Identifizierung von Hochrisikopersonen für Typ-2-Diabetes (T2DM) eingesetzt, die von Präventionsmaßnahmen profitieren. Der DIfE – DEUTSCHER DIABETES-RISIKO-TEST® (DRT [DIfE: Deutsches Institut für Ernährungsforschung Potsdam‐Rehbrücke]) wird genutzt, um das absolute 5‑Jahres-Risiko für T2DM zu bestimmen. Da die Berechnung auf nichtklinischen Informationen basiert, kann der Test unabhängig von einem Arztbesuch genutzt werden. Als Grundlage für die Entwicklung von Risikoscores dienen Daten aus prospektiven populationsbezogenen Langzeitstudien. Die sehr gute Vorhersagegüte eines Scores sollte, wie im Fall des DRT, in unabhängigen Populationen bestätigt werden. Neben dem Einsatz durch Ärzte/‑innen und zur individuellen Selbstanamnese können nichtklinische Risikoscores im Kontext breiterer, bevölkerungsbezogener Präventionskonzepte und Informationsangebote zur Senkung des Erkrankungsrisikos Anwendung finden. Durch Krankenkassen abrechenbare Präventionsleistungen sollen im Sinne des deutschen Präventionsgesetzes die Integration von gesundheitsförderndem Verhalten in den Alltag unterstützen. Obwohl Übergewicht und Ernährung relevante Lebensstilrisikofaktoren für T2DM sind, beträgt der Anteil der in Anspruch genommenen Präventionskurse in diesem Bereich nur 3 % der abgerechneten Kurse. Entsprechende Empfehlungen in ärztlichen Untersuchungen könnten eine umfangreichere Inanspruchnahme fördern. Die Verwendung von Risikoscores als Grundlage für systematische und gezielte Handlungsempfehlungen hinsichtlich einer Verhaltensprävention könnte dies, wie es bereits in Richtlinien der kardiovaskulären Prävention etabliert ist, darüber hinaus unterstützen. Auch die Weiterentwicklung der Implementationsforschung ist für den effizienten Einsatz von Risikoscores von Bedeutung. KW - Type 2 diabetes KW - preventive measures KW - risk assessment KW - life style KW - behavior KW - screening KW - Typ-2-Diabetes KW - Prävention KW - Risikoeinschätzung KW - Lebensstil KW - Verhalten Y1 - 2020 U6 - https://doi.org/10.1007/s11428-020-00592-0 SN - 1860-9716 SN - 1860-9724 VL - 16 IS - 3 SP - 226 EP - 233 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Dünkelberg, Sophie A1 - Maywald, Martina A1 - Schmitt, Anne Kristina A1 - Schwerdtle, Tanja A1 - Meyer, Sören A1 - Rink, Lothar T1 - The interaction of sodium and zinc in the priming of T cell subpopulations regarding Th17 and Treg cells JF - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology N2 - Scope: Nutrition is a critical determinant of a functional immune system. The aim of this study is to investigate the molecular mechanisms by which immune cells are influenced by zinc and sodium. Methods and Results: Mixed lymphocyte cultures and Jurkat cells are generated and incubated with zinc, sodium, or a combination of both for further tests. Zinc induces the number of regulatory T cells (Treg) and decreases T helper 17 cells (Th17), and sodium has the opposite effect. The transforming growth factor beta receptor signaling pathway is also enhanced by zinc and reduced by sodium as indicated by contrary phosphoSmad 2/3 induction. Antagonistic effects can also be seen on zinc transporter and metallothionein-1 (MT-1) mRNA expression: zinc declines Zip10 mRNA expression while sodium induces it, whereas MT-1 mRNA expression is induced by zinc while it is reduced by sodium. Conclusion: This data indicate that zinc and sodium display opposite effects regarding Treg and Th17 induction in MLC, respectively, resulting in a contrary effect on the immune system. Additionally, it reveals a direct interaction of zinc and sodium in the priming of T cell subpopulations and shows that Zip10 and MT-1 play a significant role in those differentiation pathways. KW - Foxp3 KW - regulatory T cells KW - sodium KW - T helper 17 cells KW - zinc Y1 - 2020 U6 - https://doi.org/10.1002/mnfr.201900245 SN - 1613-4133 VL - 64 IS - 2 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Kotthoff, Lisa A1 - O'Callaghan, Sarah-Louise A1 - Lisec, Jan A1 - Schwerdtle, Tanja A1 - Koch, Matthias T1 - Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry JF - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica N2 - Moxidectin (MOX) is a widely used anthelmintic drug for the treatment of internal and external parasites in food-producing and companion animals. Transformation products (TPs) of MOX, formed through metabolic degradation or acid hydrolysis, may pose a potential environmental risk, but only few were identified so far. In this study, we therefore systematically characterized electro- and photochemically generated MOX TPs using high-resolution mass spectrometry (HRMS). Oxidative electrochemical (EC) TPs were generated in an electrochemical reactor and photochemical (PC) TPs by irradiation with UV-C light. Subsequent HRMS measurements were performed to identify accurate masses and deduce occurring modification reactions of derived TPs in a suspected target analysis. In total, 26 EC TPs and 59 PC TPs were found. The main modification reactions were hydroxylation, (de-)hydration, and derivative formation with methanol for EC experiments and isomeric changes, (de-)hydration, and changes at the methoxime moiety for PC experiments. In addition, several combinations of different modification reactions were identified. For 17 TPs, we could predict chemical structures through interpretation of acquired MS/MS data. Most modifications could be linked to two specific regions of MOX. Some previously described metabolic reactions like hydroxylation or O-demethylation were confirmed in our EC and PC experiments as reaction type, but the corresponding TPs were not identical to known metabolites or degradation products. The obtained knowledge regarding novel TPs and reactions will aid to elucidate the degradation pathway of MOX which is currently unknown. KW - veterinary drug KW - moxidectin KW - transformation products KW - electrochemistry KW - photochemistry KW - LC KW - HRMS Y1 - 2020 U6 - https://doi.org/10.1007/s00216-020-02572-1 SN - 1618-2642 SN - 1618-2650 VL - 412 IS - 13 SP - 3141 EP - 3152 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Ouni, Meriem A1 - Schürmann, Annette T1 - Epigenetic contribution to obesity JF - Mammalian genome N2 - Obesity is a worldwide epidemic and contributes to global morbidity and mortality mediated via the development of nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), cardiovascular (CVD) and other diseases. It is a consequence of an elevated caloric intake, a sedentary lifestyle and a genetic as well as an epigenetic predisposition. This review summarizes changes in DNA methylation and microRNAs identified in blood cells and different tissues in obese human and rodent models. It includes information on epigenetic alterations which occur in response to fat-enriched diets, exercise and metabolic surgery and discusses the potential of interventions to reverse epigenetic modifications. Y1 - 2020 U6 - https://doi.org/10.1007/s00335-020-09835-3 SN - 0938-8990 SN - 1432-1777 VL - 31 IS - 5-6 SP - 134 EP - 145 PB - Springer CY - New York, NY ; Berlin ; Heidelberg [u.a.] ER - TY - JOUR A1 - Klaus, Susanne A1 - Ost, Mario T1 - Mitochondrial uncoupling and longevity BT - a role for mitokines? JF - Experimental gerontology N2 - Aging has been viewed both as a random process due to accumulation of molecular and cellular damage over time and as a programmed process linked to cellular pathway important for growth and maturation. These views converge on mitochondria as both the major producer of damaging reactive oxidant species (ROS) and as signaling organelles. A finite proton leak across the inner mitochondrial membrane leading to a slight uncoupling of oxidative phosphorylation and respiration is an intrinsic property of all mitochondria and according to the "uncoupling to survive" hypothesis it has evolved to protect against ROS production to minimize oxidative damage. This hypothesis is supported by evidence linking an increased endogenous, uncoupling protein (UCP1) mediated, as well as experimentally induced mitochondrial uncoupling to an increased lifespan in rodents. This is possibly due to the synergistic activation of molecular pathways linked to life extending effects of caloric restriction as well as a mitohormetic response. Mitohormesis is an adaptive stress response through mitonuclear signaling which increases stress resistance resulting in health promoting effects. Part of this response is the induction of fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), two stress-induced mitokines which elicit beneficial systemic metabolic effects via endocrine action. KW - Uncoupling proteins KW - Energy metabolism KW - Skeletal muscle KW - Mitohormesis KW - GDF15 KW - FGF21 Y1 - 2019 U6 - https://doi.org/10.1016/j.exger.2019.110796 SN - 0531-5565 SN - 1873-6815 VL - 130 PB - Elsevier Science CY - Amsterdam ER - TY - JOUR A1 - Knoche, Lisa A1 - Lisec, Jan A1 - Koch, Matthias T1 - Analysis of electrochemical and liver microsomal transformation products of lasalocid by LC/HRMS JF - Rapid communications in mass spectrometry : RCM N2 - Rationale: Lasalocid (LAS), an ionophore, is used in cattle and poultry farming as feed additive for its antibiotic and growth-promoting properties. Literature on transformation products (TP) resulting from LAS degradation is limited. So far, only hydroxylation is found to occur as the metabolic reaction during the LAS degradation. To investigate potential TPs of LAS, we used electrochemistry (EC) and liver microsome (LM) assays to synthesize TPs, which were identified using liquid chromatography high-resolution mass spectrometry (LC/HRMS). Methods: Electrochemically produced TPs were analyzed online by direct coupling of the electrochemical cell to the electrospray ionization (ESI) source of a Sciex Triple-TOF high resolution mass spectrometer. Then, EC-treated LAS solution was collected and analyzed offline using LC/HRMS to confirm stable TPs and improve their annotation with a chemical structure due to informative MS/MS spectra. In a complementary approach, TPs formed by rat and human microsomal incubation were investigated using LC/HRMS. The resulting data were used to investigate LAS modification reactions and elucidate the chemical structure of obtained TPs. Results: The online measurements identified a broad variety of TPs, resulting from modification reactions like (de-)hydrogenation, hydration, methylation, oxidation as well as adduct formation with methanol. We consistently observed different ion complexations of LAS and LAS-TPs (Na+; 2Na(+) K+; NaNH4+; KNH4+). Two stable methylated EC-TPs were found, structurally annotated, and assigned to a likely modification reaction. Using LM incubation, seven TPs were formed, mostly by oxidation/hydroxylation. After the identification of LM-TPs as Na+-complexes, we identified LM-TPs as K+-complexes. Conclusion: We identified and characterized TPs of LAS using EC- and LM-based methods. Moreover, we found different ion complexes of LAS-based TPs. This knowledge, especially the different ion complexes, may help elucidate the metabolic and environmental degradation pathways of LAS. Y1 - 2022 U6 - https://doi.org/10.1002/rcm.9349 SN - 0951-4198 SN - 1097-0231 VL - 36 IS - 18 PB - Wiley CY - New York, NY ER - TY - JOUR A1 - Cencetti, Francesca A1 - Bruno, Gennaro A1 - Bernacchioni, Caterina A1 - Japtok, Lukasz A1 - Puliti, Elisa A1 - Donati, Chiara A1 - Bruni, Paola T1 - Sphingosine 1-phosphate lyase blockade elicits myogenic differentiation of murine myoblasts acting via Spns2/S1P(2) receptor axis JF - Biochimica et biophysica acta : Molecular and cell biology of lipids N2 - The bioactive sphingolipid sphingosine 1-phosphate (S1P) has emerged in the last three decades as main regulator of key cellular processes including cell proliferation, survival, migration and differentiation. A crucial role for this sphingolipid has been recognized in skeletal muscle cell biology both in vitro and in vivo. S1P lyase (SPL) is responsible for the irreversible degradation of S1P and together with sphingosine kinases, the S1P producing enzymes, regulates cellular S1P levels. In this study is clearly showed that the blockade of SPL by pharmacological or RNA interference approaches induces myogenic differentiation of C2C12 myoblasts. Moreover, down-regulation of the specific S1P transporter spinster homolog 2 (Spns2) abrogates myogenic differentiation brought about by SPL inhibition or down-regulation, pointing at a role of extracellular S1P in the pro-myogenic action induced by SPL blockade. Furthermore, also S1P(2) receptor down-regulation was found to abrogate the pro-myogenic effect of SPL blockade. These results provide further proof that inside-out S1P signaling is critically implicated in skeletal muscle biology and provide support to the concept that the specific targeting of SPL could represent an exploitable strategy to treat skeletal muscle disorders. KW - Sphingosine 1-phosphate KW - Myogenic differentiation Y1 - 2020 U6 - https://doi.org/10.1016/j.bbalip.2020.158759 SN - 1388-1981 SN - 1879-2618 VL - 1865 IS - 9 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bishop, Christopher Allen A1 - Schulze, Matthias Bernd A1 - Klaus, Susanne A1 - Weitkunat, Karolin T1 - The branched-chain amino acids valine and leucine have differential effects on hepatic lipid metabolism JF - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology N2 - Dairy intake, as a source of branched-chain amino acids (BCAA), has been linked to a lower incidence of type-2-diabetes and increased circulating odd-chain fatty acids (OCFA). To understand this connection, we aimed to investigate differences in BCAA metabolism of leucine and valine, a possible source of OCFA, and their role in hepatic metabolism. Male mice were fed a high-fat diet supplemented with leucine and valine for 1 week and phenotypically characterized with a focus on lipid metabolism. Mouse primary hepatocytes were treated with the BCAA or a Ppar alpha activator WY-14643 to systematically examine direct hepatic effects and their mechanisms. Here, we show that only valine supplementation was able to increase hepatic and circulating OCFA levels via two pathways; a PPAR alpha-dependent induction of alpha-oxidation and an increased supply of propionyl-CoA for de novo lipogenesis. Meanwhile, we were able to confirm leucine-mediated effects on the inhibition of food intake and transport of fatty acids, as well as induction of S6 ribosomal protein phosphorylation. Taken together, these data illustrate differential roles of the BCAA in lipid metabolism and provide preliminary evidence that exclusively valine contributes to the endogenous formation of OCFA which is important for a better understanding of these metabolites in metabolic health. KW - fatty acid metabolism KW - leucine KW - liver KW - OCFA KW - valine Y1 - 2020 U6 - https://doi.org/10.1096/fj.202000195R SN - 0892-6638 SN - 1530-6860 VL - 34 IS - 7 SP - 9727 EP - 9739 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Schedlbauer, Carola A1 - Blaue, Dominique A1 - Raila, Jens A1 - Vervuert, Ingrid T1 - Alterations of serum vitamin E and vitamin A concentrations of ponies and horses during experimentally induced obesity JF - Journal of animal physiology and animal nutrition JF - Zeitschrift für Tierphysiologie, Tierernährung und Futtermittelkunde N2 - Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum alpha-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (+/- SD) % BW gain achieved during two years of excess energy intake was 29.9 +/- 19.4% for ponies and 17 +/- 6.74% for horses. Serum alpha-tocopherol increased significantly in ponies and horses during excess energy intake and circulating alpha-tocopherol levels correlated positively with alpha-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation. KW - body weight gain KW - equine KW - laminitis KW - retinol-binding protein 4 KW - alpha-tocopherol Y1 - 2020 U6 - https://doi.org/10.1111/jpn.13385 SN - 0931-2439 SN - 1439-0396 VL - 104 IS - 5 SP - 1501 EP - 1508 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Wiedmer, Petra A1 - Jung, Tobias A1 - Castro, Jose Pedro A1 - Pomatto, Laura C. D. A1 - Sun, Patrick Y. A1 - Davies, Kelvin J. A. A1 - Grune, Tilman T1 - Sarcopenia BT - molecular mechanisms and open questions JF - Ageing research reviews : ARR N2 - Sarcopenia represents a muscle-wasting syndrome characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, and strength occurring during normal aging. Sarcopenia patients are mainly suffering from the loss in muscle strength and are faced with mobility disorders reducing their quality of life and are, therefore, at higher risk for morbidity (falls, bone fracture, metabolic diseases) and mortality.
Several molecular mechanisms have been described as causes for sarcopenia that refer to very different levels of muscle physiology. These mechanisms cover e. g. function of hormones (e. g. IGF-1 and Insulin), muscle fiber composition and neuromuscular drive, myo-satellite cell potential to differentiate and proliferate, inflammatory pathways as well as intracellular mechanisms in the processes of proteostasis and mitochondrial function.
In this review, we describe sarcopenia as a muscle-wasting syndrome distinct from other atrophic diseases and summarize the current view on molecular causes of sarcopenia development as well as open questions provoking further research efforts for establishing efficient lifestyle and therapeutic interventions. KW - molecular pathways KW - proteostasis KW - proteasome KW - autophagy KW - mitochondria, KW - muscle fibre composition Y1 - 2020 U6 - https://doi.org/10.1016/j.arr.2020.101200 SN - 1568-1637 SN - 1872-9649 VL - 65 PB - Elsevier CY - Clare ER -