@article{LiShenZhangetal.2022, author = {Li, Jian and Shen, Jinhua and Zhang, Xiaoli and Peng, Yangqin and Zhang, Qin and Hu, Liang and Reichetzeder, Christoph and Zeng, Suimin and Li, Jing and Tian, Mei and Gong, Fei and Lin, Ge and Hocher, Berthold}, title = {Risk factors associated with preterm birth after IVF/ICSI}, series = {Scientific reports}, volume = {12}, journal = {Scientific reports}, number = {1}, publisher = {Nature Research}, address = {Berlin}, issn = {2045-2322}, doi = {10.1038/s41598-022-12149-w}, pages = {9}, year = {2022}, abstract = {In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd-37th gestational week) and early preterm birth (20th-32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (< 25) maternal age (OR: 1.504, 95\% CI 1.108-2.042, P = 0.009; OR: 2.125, 95\% CI 1.049-4.304, P = 0.036, respectively), multiple pregnancy (OR: 9.780, 95\% CI 8.014-11.935, P < 0.001; OR: 8.588, 95\% CI 4.866-15.157, P < 0.001, respectively), placenta previa (OR: 14.954, 95\% CI 8.053-27.767, P < 0.001; OR: 16.479, 95\% CI 4.381-61.976, P < 0.001, respectively), and embryo reduction (OR: 3.547, 95\% CI 1.736-7.249, P = 0.001; OR: 7.145, 95\% CI 1.990-25.663, P = 0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95\% CI 1.770-3.514, P < 0.001), elevated triglycerides (OR: 1.120, 95\% CI 1.011-1.240, P = 0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95\% CI 0.949-0.985, P < 0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor.}, language = {en} } @article{PolemitiBaudryKuxhausetal.2021, author = {Polemiti, Elli and Baudry, Julia and Kuxhaus, Olga and J{\"a}ger, Susanne and Bergmann, Manuela and Weikert, Cornelia and Schulze, Matthias B.}, title = {BMI and BMI change following incident type 2 diabetes and risk of microvascular and macrovascular complications}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, volume = {64}, journal = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, number = {4}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {0012-186X}, doi = {10.1007/s00125-020-05362-7}, pages = {814 -- 825}, year = {2021}, abstract = {Aims/hypothesis Studies suggest decreased mortality risk among people who are overweight or obese compared with individuals with normal weight in type 2 diabetes (obesity paradox). However, the relationship between body weight or weight change and microvascular vs macrovascular complications of type 2 diabetes remains unresolved. We investigated the association between BMI and BMI change with long-term risk of microvascular and macrovascular complications in type 2 diabetes in a prospective cohort study. Methods We studied participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, who were free of cancer, cardiovascular disease and microvascular disease at diagnosis (n = 1083). Pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI were evaluated in multivariable-adjusted Cox models. Results There were 85 macrovascular (myocardial infarction and stroke) and 347 microvascular events (kidney disease, neuropathy and retinopathy) over a median follow-up of 10.8 years. Median pre-diagnosis BMI was 29.9 kg/m(2) (IQR 27.4-33.2), and the median relative annual BMI change was -0.4\% (IQR -2.1 to 0.9). Higher pre-diagnosis BMI was positively associated with total microvascular complications (multivariable-adjusted HR per 5 kg/m(2) [95\% CI]: 1.21 [1.07, 1.36], kidney disease 1.39 [1.21, 1.60] and neuropathy 1.12 [0.96, 1.31]) but not with macrovascular complications (HR 1.05 [95\% CI 0.81, 1.36]). Analyses according to BMI categories corroborated these findings. Effect modification was not evident by sex, smoking status or age groups. In analyses according to BMI change categories, BMI loss of more than 1\% indicated a decreased risk of total microvascular complications (HR 0.62 [95\% CI 0.47, 0.80]), kidney disease (HR 0.57 [95\% CI 0.40, 0.81]) and neuropathy (HR 0.73 [95\% CI 0.52, 1.03]), compared with participants with a stable BMI; no clear association was observed for macrovascular complications (HR 1.04 [95\% CI 0.62, 1.74]). The associations between BMI gain compared with stable BMI and diabetes-related vascular complications were less apparent. Associations were consistent across strata of sex, age, pre-diagnosis BMI or medication but appeared to be stronger among never-smokers compared with current or former smokers. Conclusions/interpretation Among people with incident type 2 diabetes, pre-diagnosis BMI was positively associated with microvascular complications, while a reduced risk was observed with weight loss when compared with stable weight. The relationships with macrovascular disease were less clear.}, language = {en} } @article{HocherLuReichetzederetal.2022, author = {Hocher, Berthold and Lu, Yong-Ping and Reichetzeder, Christoph and Zhang, Xiaoli and Tsuprykov, Oleg and Rahnenf{\"u}hrer, Jan and Xie, Li and Li, Jian and Hu, Liang and Kr{\"a}mer, Bernhard K. and Hasan, Ahmed A.}, title = {Paternal eNOS deficiency in mice affects glucose homeostasis and liver glycogen in male offspring without inheritance of eNOS deficiency itself}, series = {Diabetologia}, volume = {65}, journal = {Diabetologia}, number = {7}, publisher = {Springer}, address = {New York}, issn = {0012-186X}, doi = {10.1007/s00125-022-05700-x}, pages = {1222 -- 1236}, year = {2022}, abstract = {Aims/hypothesis It was shown that maternal endothelial nitric oxide synthase (eNOS) deficiency causes fatty liver disease and numerically lower fasting glucose in female wild-type offspring, suggesting that parental genetic variants may influence the offspring's phenotype via epigenetic modifications in the offspring despite the absence of a primary genetic defect. The aim of the current study was to analyse whether paternal eNOS deficiency may cause the same phenotype as seen with maternal eNOS deficiency. Methods Heterozygous (+/-) male eNOS (Nos3) knockout mice or wild-type male mice were bred with female wild-type mice. The phenotype of wild-type offspring of heterozygous male eNOS knockout mice was compared with offspring from wild-type parents. Results Global sperm DNA methylation decreased and sperm microRNA pattern altered substantially. Fasting glucose and liver glycogen storage were increased when analysing wild-type male and female offspring of +/- eNOS fathers. Wild-type male but not female offspring of +/- eNOS fathers had increased fasting insulin and increased insulin after glucose load. Analysing candidate genes for liver fat and carbohydrate metabolism revealed that the expression of genes encoding glucocorticoid receptor (Gr; also known as Nr3c1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1a; also known as Ppargc1a) was increased while DNA methylation of Gr exon 1A and Pgc1a promoter was decreased in the liver of male wild-type offspring of +/- eNOS fathers. The endocrine pancreas in wild-type offspring was not affected.
Conclusions/interpretation Our study suggests that paternal genetic defects such as eNOS deficiency may alter the epigenome of the sperm without transmission of the paternal genetic defect itself. In later life wild-type male offspring of +/- eNOS fathers developed increased fasting insulin and increased insulin after glucose load. These effects are associated with increased Gr and Pgc1a gene expression due to altered methylation of these genes.}, language = {en} } @article{KoelmanHuybrechtsBiesbroeketal.2022, author = {Koelman, Liselot A. and Huybrechts, Inge and Biesbroek, Sander and van 't Veer, Pieter and Schulze, Matthias Bernd and Aleksandrova, Krasimira}, title = {Dietary choices impact on greenhouse gas emissions}, series = {Sustainability / Multidisciplinary Digital Publishing Institute (MDPI)}, volume = {14}, journal = {Sustainability / Multidisciplinary Digital Publishing Institute (MDPI)}, number = {7}, publisher = {MDPI}, address = {Basel}, issn = {2071-1050}, doi = {10.3390/su14073854}, pages = {10}, year = {2022}, abstract = {The present study estimated diet-related greenhouse gas emissions (GHGE) and land use (LU) in a sample of adults, examined main dietary contributors of GHGE, and evaluated socio demographic, lifestyle, and wellbeing factors as potential determinants of high environmental impact. A cross-sectional design based on data collected from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (2010-2012) was used. Usual diet was assessed using food frequency questionnaires. Diet-related GHGE and LU were calculated using a European-average lifecycle analyses-food-item database (SHARP-ID). Information on potential determinants were collected using self-administered questionnaires. Men (n = 404) and women (n = 401) at an average age of 66.0 +/- 8.4 years were included. Dietary-related energy-adjusted GHGE in men was 6.6 +/- 0.9 and in women was 7.0 +/- 1.1 kg CO2 eq per 2000 kcal. LU in men was 7.8 +/- 1.2 and in women was 7.7 +/- 1.2 m(2)/year per 2000 kcal. Food groups contributing to most GHGE included dairy, meat and non-alcoholic beverages. Among women, being single, having a job, being a smoker and having higher BMI were characteristics associated with higher GHGE, whereas for men these included being married, longer sleeping duration and higher BMI. Further studies are warranted to provide insights into population-specific determinants of sustainable dietary choices.}, language = {en} } @article{MaharjanSinghHanifetal.2022, author = {Maharjan, Romi Singh and Singh, Ajay Vikram and Hanif, Javaria and Rosenkranz, Daniel and Haidar, Rashad and Shelar, Amruta and Singh, Shubham Pratap and Dey, Aditya and Patil, Rajendra and Zamboni, Paolo and Laux, Peter and Luch, Andreas}, title = {Investigation of the associations between a nanomaterial's microrheology and toxicology}, series = {ACS omega / American Chemical Society}, volume = {7}, journal = {ACS omega / American Chemical Society}, number = {16}, publisher = {ACS Publications}, address = {Washington, DC}, issn = {2470-1343}, doi = {10.1021/acsomega.2c00472}, pages = {13985 -- 13997}, year = {2022}, abstract = {With the advent of Nanotechnology, the use of nanomaterials in consumer products is increasing on a daily basis, due to which a deep understanding and proper investigation regarding their safety and risk assessment should be a major priority. To date, there is no investigation regarding the microrheological properties of nanomaterials (NMs) in biological media. In our study, we utilized in silico models to select the suitable NMs based on their physicochemical properties such as solubility and lipophilicity. Then, we established a new method based on dynamic light scattering (DLS) microrheology to get the mean square displacement (MSD) and viscoelastic property of two model NMs that are dendrimers and cerium dioxide nanoparticles in Dulbecco's Modified Eagle Medium (DMEM) complete media at three different concentrations for both NMs. Subsequently, we established the cytotoxicological profiling using water-soluble tetrazolium salt-1 (WST-1) and a reactive oxygen species (ROS) assay. To take one step forward, we further looked into the tight junction properties of the cells using immunostaining with Zonula occluden-1 (ZO-1) antibodies and found that the tight junction function or transepithelial resistance (TEER) was affected in response to the microrheology and cytotoxicity. The quantitative polymerase chain reaction (q-PCR) results in the gene expression of ZO-1 after the 24 h treatment with NPs further validates the findings of immunostaining results. This new method that we established will be a reference point for other NM studies which are used in our day-to-day consumer products.}, language = {en} } @article{JohannKleinertKlaus2021, author = {Johann, Kornelia and Kleinert, Maximilian and Klaus, Susanne}, title = {The role of GDF15 as a myomitokine}, series = {Cells}, volume = {10}, journal = {Cells}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2073-4409}, doi = {10.3390/cells10112990}, pages = {16}, year = {2021}, abstract = {Growth differentiation factor 15 (GDF15) is a cytokine best known for affecting systemic energy metabolism through its anorectic action. GDF15 expression and secretion from various organs and tissues is induced in different physiological and pathophysiological states, often linked to mitochondrial stress, leading to highly variable circulating GDF15 levels. In skeletal muscle and the heart, the basal expression of GDF15 is very low compared to other organs, but GDF15 expression and secretion can be induced in various stress conditions, such as intense exercise and acute myocardial infarction, respectively. GDF15 is thus considered as a myokine and cardiokine. GFRAL, the exclusive receptor for GDF15, is expressed in hindbrain neurons and activation of the GDF15-GFRAL pathway is linked to an increased sympathetic outflow and possibly an activation of the hypothalamic-pituitary-adrenal (HPA) stress axis. There is also evidence for peripheral, direct effects of GDF15 on adipose tissue lipolysis and possible autocrine cardiac effects. Metabolic and behavioral outcomes of GDF15 signaling can be beneficial or detrimental, likely depending on the magnitude and duration of the GDF15 signal. This is especially apparent for GDF15 production in muscle, which can be induced both by exercise and by muscle disease states such as sarcopenia and mitochondrial myopathy.}, language = {en} } @article{MenzelLongreeAbrahametal.2022, author = {Menzel, Juliane and Longree, Alessa and Abraham, Klaus and Schulze, Matthias Bernd and Weikert, Cornelia}, title = {Dietary and plasma phospholipid profiles in vegans and omnivores-results from the RBVD study}, series = {Nutrients}, volume = {14}, journal = {Nutrients}, number = {14}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu14142900}, pages = {13}, year = {2022}, abstract = {Over the last few years, the vegan diet has become increasingly popular in Germany. It has been proposed that this diet is generally lower in fat, but less is known about the impact on fatty acid (FA) profiles. Therefore, the cross-sectional "Risks and Benefits of a Vegan Diet" (RBVD) study (n = 72) was used to investigate dietary FA intake as well as plasma phospholipid FA in vegans (n = 36) compared to omnivores (n = 36). Vegans had a significantly lower dietary intake of total fat (median 86 g/day, IQR 64-111) in comparison to omnivores (median 104 g/day, IQR 88-143, p = 0.004). Further, vegans had a lower intake of saturated fatty acids (SFA) (p < 0.0001) and monounsaturated fatty acids (MUFA) (p = 0.001) compared to omnivores. Vegans had a higher intake in total polyunsaturated fatty acids (PUFA), omega-3 and omega-6 PUFA compared to omnivores, but without statistical significance after Bonferroni correction. According to plasma phospholipid profiles, relatively lower proportions of SFA (p < 0.0001), total trans fatty acids (TFA) (p = 0.0004) and omega-3-FA (p < 0.0001), but higher proportions of omega-6-FA (p < 0.0001) were observed in vegans. With the exception of omega-3 PUFA, a vegan diet is associated with a more favorable dietary fat intake and more favorable plasma FA profiles and therefore may reduce cardiovascular risk.}, language = {en} } @misc{HerpichMuellerWerdanNorman2022, author = {Herpich, Catrin and M{\"u}ller-Werdan, Ursula and Norman, Kristina}, title = {Role of plant-based diets in promoting health and longevity}, series = {Maturitas : The European menopause journal}, volume = {165}, journal = {Maturitas : The European menopause journal}, publisher = {Elsevier Science}, address = {Amsterdam [u.a.]}, issn = {0378-5122}, doi = {10.1016/j.maturitas.2022.07.003}, pages = {47 -- 51}, year = {2022}, abstract = {Western-style obesity-promoting diets are associated with increased inflammation, higher disease incidence and mortality. In contrast, plant-based diets (PBDs), which incorporate large amounts of vegetables and fruit, legumes, whole grains and only a small amount of meat, are generally associated with better health and lower mortality. This narrative review summarizes the evidence on health and life span in adults adhering to PBDs and discusses the potentially longevity-promoting mechanism of PBDs as well as limitations due to nutrient deficiencies. Epidemiologic studies consistently report lower mortality rates in adults who adhering to PBDs when compared with people whose diet regularly includes meat. PBDs are associated with many health benefits, such as improved metabolic and inflammatory profile. In turn, the incidence of cardiovascular disease is lower in adults consuming PBDs, which contributes to their better health. The health-promoting effects of PBDs are still not entirely clear but most likely multifactorial and include modulation of the gut microbiome. The interest in possible longevity-promoting mechanisms of PBDs has increased in recent years, as many characteristics of PBDs such as protein restriction and restriction of certain amino acids are known to extend the life span. While there is ample evidence from animal studies, large-scale human studies, which also provide insight into the specific mechanisms of the effect of PBDs on longevity, are missing. However, due to the lower protein content of PBDs, there appears to be an age limit for the anticipated health effects, as adults over 65 require larger amounts of protein.}, language = {en} } @article{BirukovPolemitiJaegeretal.2022, author = {Birukov, Anna and Polemiti, Elli and Jaeger, Susanne and Stefan, Norbert and Schulze, Matthias Bernd}, title = {Fetuin-A and risk of diabetes-related vascular complications}, series = {Cardiovascular diabetology}, volume = {21}, journal = {Cardiovascular diabetology}, number = {1}, publisher = {BMC}, address = {London}, issn = {1475-2840}, doi = {10.1186/s12933-021-01439-8}, pages = {11}, year = {2022}, abstract = {Background Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes. It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. Methods Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years). Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. Results In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95\% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). Conclusions Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.}, language = {en} } @article{SilvaOliveiraCostaTchewonpietal.2021, author = {Silva, Bibiana and Oliveira Costa, Ana Carolina and Tchewonpi, Sorel Sagu and B{\"o}nick, Josephine and Huschek, Gerd and Gonzaga, Luciano Valdemiro and Fett, Roseane and Baldermann, Susanne and Rawel, Harshadrai Manilal}, title = {Comparative quantification and differentiation of bracatinga (Mimosa scabrella Bentham) honeydew honey proteins using targeted peptide markers identified by high-resolution mass spectrometry}, series = {Food research international}, volume = {141}, journal = {Food research international}, publisher = {Elsevier}, address = {New York, NY [u.a.]}, issn = {0963-9969}, doi = {10.1016/j.foodres.2020.109991}, pages = {10}, year = {2021}, abstract = {Honey traceability is an important topic, especially for honeydew honeys, due to the increased incidence of adulteration. This study aimed to establish specific markers to quantify proteins in honey. A proteomics strategy to identify marker peptides from bracatinga honeydew honey was therefore developed. The proteomics approach was based on initial untargeted identification of honey proteins and peptides by LC-ESI-Triple-TOF-MS/MS, which identified the major royal jelly proteins (MRJP) presence. Afterwards, the peptides were selected by the in silico digestion. The marker peptides were quantified by the developed targeted LC-QqQ-MS/MS method, which provided good linearity and specificity, besides recoveries between 92 and 100\% to quantify peptides from bracatinga honeydew honey. The uniqueness and high response in mass spectrometry were backed by further complementary protein analysis (SDS-PAGE). The selected marker peptides EALPHVPIFDR (MRJP 1), ILGANVK (MRJP 2), TFVTIER (MRJP 3), QNIDVVAR (MRJP 4), FINNDYNFNEVNFR (MRJP 5) and LLQPYPDWSWTK (MRJP 7), quantified by LC-QqQ-MS/MS, highlighted that the content of QNIDVVAR from MRJP 4 could be used to differentiate bracatinga honeydew honey from floral honeys (p < 0.05) as a potential marker for its authentication. Finally, principal components analysis highlighted the QNIDVVAR content as a good descriptor of the analyzed bracatinga honeydew honey samples.}, language = {en} } @article{IjomoneIroegbuMorcilloetal.2022, author = {Ijomone, Omamuyovwi M. and Iroegbu, Joy D. and Morcillo, Patricia and Ayodele, Akinyemi J. and Ijomone, Olayemi K. and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael}, title = {Sex-dependent metal accumulation and immunoexpression of Hsp70 and Nrf2 in rats' brain following manganese exposure}, series = {Environmental toxicology}, volume = {37}, journal = {Environmental toxicology}, number = {9}, publisher = {Wiley}, address = {New York, NY}, issn = {1520-4081}, doi = {10.1002/tox.23583}, pages = {2167 -- 2177}, year = {2022}, abstract = {Manganese (Mn), although important for multiple cellular processes, has posed environmental health concerns due to its neurotoxic effects. In recent years, there have been extensive studies on the mechanism of Mn-induced neuropathology, as well as the sex-dependent vulnerability to its neurotoxic effects. Nonetheless, cellular mechanisms influenced by sex differences in susceptibility to Mn have yet to be adequately characterized. Since oxidative stress is a key mechanism of Mn neurotoxicity, here, we have probed Hsp70 and Nrf2 proteins to investigate the sex-dependent changes following exposure to Mn. Male and female rats were administered intraperitoneal injections of MnCl2 (10 mg/kg and 25 mg/kg) 48 hourly for a total of eight injections (15 days). We evaluated changes in body weight, as well as Mn accumulation, Nrf2 and Hsp70 expression across four brain regions; striatum, cortex, hippocampus and cerebellum in both sexes. Our results showed sex-specific changes in body-weight, specifically in males but not in females. Additionally, we noted sex-dependent accumulation of Mn in the brain, as well as in expression levels of Nrf2 and Hsp70 proteins. These findings revealed sex-dependent susceptibility to Mn-induced neurotoxicity corresponding to differential Mn accumulation, and expression of Hsp70 and Nrf2 across several brain regions.}, language = {en} } @article{EichelmannSellemWittenbecheretal.2022, author = {Eichelmann, Fabian and Sellem, Laury and Wittenbecher, Clemens and J{\"a}ger, Susanne and Kuxhaus, Olga and Prada, Marcela and Cuadrat, Rafael and Jackson, Kim G. and Lovegrove, Julie A. and Schulze, Matthias Bernd}, title = {Deep lipidomics in human plasma: cardiometabolic disease risk and effect of dietary fat modulation}, series = {Circulation}, volume = {146}, journal = {Circulation}, number = {1}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0009-7322}, doi = {10.1161/CIRCULATIONAHA.121.056805}, pages = {21 -- 35}, year = {2022}, abstract = {Background: In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. Methods: The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. Results: Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95\% CI, 0.5-0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95\% CI, 0.4-0.7) SD units. Conclusions: We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.}, language = {en} } @article{BeckmannSchumacherKleuseretal.2021, author = {Beckmann, Nadine and Schumacher, Fabian and Kleuser, Burkhard and Gulbins, Erich and Nomellini, Vanessa and Caldwell, Charles C.}, title = {Burn injury impairs neutrophil chemotaxis through increased ceramide}, series = {Shock : injury, inflammation, and sepsis, laboratory and clinical approaches}, volume = {56}, journal = {Shock : injury, inflammation, and sepsis, laboratory and clinical approaches}, number = {1}, publisher = {Lippincott Williams \& Wilkins}, address = {Hagerstown, Md.}, issn = {1073-2322}, doi = {10.1097/SHK.0000000000001693}, pages = {125 -- 132}, year = {2021}, abstract = {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.}, language = {en} } @article{SeidelJacobsKohlTamayoetal.2022, author = {Seidel-Jacobs, Esther and Kohl, Fiona and Tamayo, Miguel and Rosenbauer, Joachim and Schulze, Matthias Bernd and Kuss, Oliver and Rathmann, Wolfgang}, title = {Impact of applying a diabetes risk score in primary care on change in physical activity}, series = {Acta diabetologica}, volume = {59}, journal = {Acta diabetologica}, number = {8}, publisher = {Springer}, address = {Mailand}, issn = {0940-5429}, doi = {10.1007/s00592-022-01895-y}, pages = {1031 -- 1040}, year = {2022}, abstract = {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).}, language = {en} } @article{SolovyevDrobyshevBlumeetal.2021, author = {Solovyev, Nikolay and Drobyshev, Evgenii and Blume, Bastian and Michalke, Bernhard}, title = {Selenium at the neural barriers}, series = {Frontiers in neuroscience / Frontiers Research Foundation}, volume = {15}, journal = {Frontiers in neuroscience / Frontiers Research Foundation}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1662-453X}, doi = {10.3389/fnins.2021.630016}, pages = {18}, year = {2021}, abstract = {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.}, language = {en} } @article{HoffmannOttRaupbachetal.2022, author = {Hoffmann, Holger and Ott, Christiane and Raupbach, Jana and Andernach, Lars and Renz, Matthias and Grune, Tilman and Hanschen, Franziska S.}, title = {Assessing bioavailability and bioactivity of 4-Hydroxythiazolidine-2-Thiones, newly discovered glucosinolate degradation products formed during domestic boiling of cabbage}, series = {Frontiers in nutrition}, volume = {9}, journal = {Frontiers in nutrition}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {2296-861X}, doi = {10.3389/fnut.2022.941286}, pages = {13}, year = {2022}, abstract = {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.}, language = {en} } @article{DelperoArendsSprechertetal.2022, author = {Delpero, Manuel and Arends, Danny and Sprechert, Maximilian and Krause, Florian and Kluth, Oliver and Sch{\"u}rmann, Annette and Brockmann, Gudrun A. and Hesse, Deike}, title = {Identification of four novel QTL linked to the metabolic syndrome in the Berlin Fat Mouse}, series = {International journal of obesity / North American Association for the Study of Obesity}, volume = {46}, journal = {International journal of obesity / North American Association for the Study of Obesity}, number = {2}, publisher = {Nature Publ. Group}, address = {Avenel, NJ}, issn = {0307-0565}, doi = {10.1038/s41366-021-00991-3}, pages = {307 -- 315}, year = {2022}, abstract = {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.}, language = {en} } @article{MuehlenbruchZhuoBardenheieretal.2019, author = {M{\"u}hlenbruch, Kristin and Zhuo, Xiaohui and Bardenheier, Barbara and Shao, Hui and Laxy, Michael and Icks, Andrea and Zhang, Ping and Gregg, Edward W. and Schulze, Matthias Bernd}, title = {Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention}, series = {Acta Diabetologica}, volume = {57}, journal = {Acta Diabetologica}, number = {4}, publisher = {Springer}, address = {Mailand}, issn = {0001-5563}, doi = {10.1007/s00592-019-01451-1}, pages = {447 -- 454}, year = {2019}, abstract = {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.}, language = {en} } @article{DoellDjalaliFarahaniKofoetZrenneretal.2021, author = {D{\"o}ll, Stefanie and Djalali Farahani-Kofoet, Roxana and Zrenner, Rita and Henze, Andrea and Witzel, Katja}, title = {Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates}, series = {Horticulture research}, volume = {8}, journal = {Horticulture research}, number = {1}, publisher = {Nanjing Agricultural Univ.}, address = {Nanjing}, issn = {2052-7276}, doi = {10.1038/s41438-021-00510-5}, pages = {14}, year = {2021}, abstract = {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.}, language = {en} } @article{KuhnTavaresJacquesTeixeiraetal.2021, author = {Kuhn, Eug{\^e}nia Carla and Tavares Jacques, Maur{\´i}cio and Teixeira, Daniela and Meyer, S{\"o}ren and Gralha, Thiago and Roehrs, Rafael and Camargo, Sandro and Schwerdtle, Tanja and Bornhorst, Julia and {\´A}vila, Daiana Silva}, title = {Ecotoxicological assessment of Uruguay River and affluents pre- and biomonitoring}, series = {Environmental science and pollution research : ESPR}, volume = {28}, journal = {Environmental science and pollution research : ESPR}, number = {17}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {0944-1344}, doi = {10.1007/s11356-020-11986-4}, pages = {21730 -- 21741}, year = {2021}, abstract = {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.}, language = {en} } @article{PanMaLiuetal.2021, author = {Pan, Yuanwei and Ma, Xuehua and Liu, Chuang and Xing, Jie and Zhou, Suqiong and Parshad, Badri and Schwerdtle, Tanja and Li, Wenzhong and Wu, Aiguo and Haag, Rainer}, title = {Retinoic acid-loaded dendritic polyglycerol-conjugated gold nanostars for targeted photothermal therapy in breast cancer stem cells}, series = {ACS nano}, volume = {15}, journal = {ACS nano}, number = {9}, publisher = {American Chemical Society}, address = {Washington}, issn = {1936-0851}, doi = {10.1021/acsnano.1c05452}, pages = {15069 -- 15084}, year = {2021}, abstract = {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.}, language = {en} } @phdthesis{Rinne2024, author = {Rinne, Theresa Charlotte}, title = {The effects of nutrients on bone stem cell function and regeneration}, school = {Universit{\"a}t Potsdam}, pages = {V, 134}, year = {2024}, abstract = {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.}, language = {en} } @article{SellemAntoniKoutsosetal.2022, author = {Sellem, Laury and Antoni, Rona and Koutsos, Athanasios and Ozen, Ezgi and Wong, Gloria and Ayyad, Hasnaa and Weech, Michelle and Schulze, Matthias Bernd and Wernitz, Andreas and Fielding, Barbara A. and Robertson, M. Denise and Jackson, Kim G. and Griffin, Bruce A. and Lovegrove, Julie A.}, title = {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}, series = {European journal of nutrition}, volume = {61}, journal = {European journal of nutrition}, number = {7}, publisher = {Springer}, address = {Heidelberg}, issn = {1436-6207}, doi = {10.1007/s00394-022-02910-2}, pages = {3669 -- 3684}, year = {2022}, abstract = {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.}, language = {en} } @inproceedings{MichaelisAengenheisterSchwerdtleetal.2021, author = {Michaelis, Vivien and Aengenheister, Leonie and Schwerdtle, Tanja and Buerki-Thurnherr, Tina and Bornhorst, Julia}, title = {Manganese translocation across an in vitro model of human villous trophoblast}, series = {Placenta}, volume = {112}, booktitle = {Placenta}, publisher = {Elsevier}, address = {Amsterdam [u.a.]}, issn = {0143-4004}, doi = {10.1016/j.placenta.2021.07.205}, pages = {E63 -- E64}, year = {2021}, language = {en} } @article{JannaschNickelSchulze2021, author = {Jannasch, Franziska and Nickel, Daniela and Schulze, Matthias Bernd}, title = {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}, series = {British journal of nutrition : BJN : an international journal of nutritional science / published on behalf of The Nutrition Society}, volume = {125}, journal = {British journal of nutrition : BJN : an international journal of nutritional science / published on behalf of The Nutrition Society}, number = {11}, publisher = {Cambridge University Press}, address = {Cambridge}, issn = {1475-2662}, doi = {10.1017/S0007114520003517}, pages = {1270 -- 1280}, year = {2021}, abstract = {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.}, language = {en} } @article{VaraoMouraAparecidoRosiniSilvaDomingosSantodaSilvaetal.2022, author = {Var{\~a}o Moura, Alexandre and Aparecido Rosini Silva, Alex and Domingos Santo da Silva, Jos{\´e} and Aleixo Leal Pedroza, Lucas and Bornhorst, Julia and Stiboller, Michael and Schwerdtle, Tanja and Gubert, Priscila}, title = {Determination of ions in Caenorhabditis elegans by ion chromatography}, series = {Journal of chromatography. B}, volume = {1204}, journal = {Journal of chromatography. B}, publisher = {Elsevier}, address = {Amsterdam [u.a.]}, issn = {1570-0232}, doi = {10.1016/j.jchromb.2022.123312}, pages = {6}, year = {2022}, abstract = {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.}, language = {en} } @article{SchmiedeskampSchreinerBaldermann2022, author = {Schmiedeskamp, Amy and Schreiner, Monika and Baldermann, Susanne}, title = {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.)}, series = {Journal of agricultural and food chemistry : a publication of the American Chemical Society}, volume = {70}, journal = {Journal of agricultural and food chemistry : a publication of the American Chemical Society}, number = {5}, publisher = {American Chemical Society}, address = {Washington}, issn = {0021-8561}, doi = {10.1021/acs.jafc.1c05718}, pages = {1629 -- 1639}, year = {2022}, abstract = {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.}, language = {en} } @article{JonasKluthHelmsetal.2022, author = {Jonas, Wenke and Kluth, Oliver and Helms, Anett and Voss, Sarah and Jahnert, Markus and Gottmann, Pascal and Speckmann, Thilo and Knebel, Birgit and Chadt, Alexandra and Al-Hasani, Hadi and Sch{\"u}rmann, Annette and Vogel, Heike}, title = {Identification of novel genes involved in hyperglycemia in mice}, series = {International journal of molecular sciences}, volume = {23}, journal = {International journal of molecular sciences}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {1661-6596}, doi = {10.3390/ijms23063205}, pages = {13}, year = {2022}, abstract = {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.}, language = {en} } @article{FitznerFrickeSchreineretal.2021, author = {Fitzner, Maria and Fricke, Anna and Schreiner, Monika and Baldermann, Susanne}, title = {Utilization of regional natural brines for the indoor cultivation of Salicornia europaea}, series = {Sustainability / Multidisciplinary Digital Publishing Institute (MDPI)}, volume = {13}, journal = {Sustainability / Multidisciplinary Digital Publishing Institute (MDPI)}, number = {21}, publisher = {MDPI}, address = {Basel}, issn = {2071-1050}, doi = {10.3390/su132112105}, pages = {12}, year = {2021}, abstract = {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.}, language = {en} } @article{WiggerSchumacherSchneiderSchauliesetal.2021, author = {Wigger, Dominik and Schumacher, Fabian and Schneider-Schaulies, Sibylle and Kleuser, Burkhard}, title = {Sphingosine 1-phosphate metabolism and insulin signaling}, series = {Cellular signalling}, volume = {82}, journal = {Cellular signalling}, publisher = {Elsevier Science}, address = {Amsterdam [u.a.]}, issn = {0898-6568}, doi = {10.1016/j.cellsig.2021.109959}, pages = {16}, year = {2021}, abstract = {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.}, language = {en} } @phdthesis{Henning2024, author = {Henning, Thorsten}, title = {Cross-sectional associations of dietary biomarker patterns with health and nutritional status}, school = {Universit{\"a}t Potsdam}, pages = {111}, year = {2024}, language = {en} } @article{DwiPutraReichetzederHasanetal.2020, author = {Dwi Putra, Sulistyo Emantoko and Reichetzeder, Christoph and Hasan, Ahmed Abdallah Abdalrahman Mohamed and Slowinski, Torsten and Chu, Chang and Kr{\"a}mer, Bernhard K. and Kleuser, Burkhard and Hocher, Berthold}, title = {Being born large for gestational age is associated with increased global placental DNA methylation}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-020-57725-0}, pages = {1 -- 10}, year = {2020}, abstract = {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).}, language = {en} } @article{LangBohnBhatetal.2020, author = {Lang, Judith and Bohn, Patrick and Bhat, Hilal and Jastrow, Holger and Walkenfort, Bernd and Cansiz, Feyza and Fink, Julian and Bauer, Michael and Schumacher, Fabian and Kleuser, Burkhard and Lang, Karl S.}, title = {Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group UK}, address = {London}, issn = {2041-1723}, doi = {10.1038/s41467-020-15072-8}, pages = {1 -- 15}, year = {2020}, abstract = {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.}, language = {en} } @article{HarmsScalbertZamoraRosetal.2019, author = {Harms, Laura M. and Scalbert, Augustin and Zamora-Ros, Raul and Rinaldi, Sabina and Jenab, Mazda and Murphy, Neil and Achaintre, David and Tj{\o}nneland, Anne and Olsen, Anja and Overvad, Kim and Aleksandrova, Krasimira}, title = {Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations}, series = {British Journal of Nutrition}, volume = {123}, journal = {British Journal of Nutrition}, number = {2}, publisher = {Cambridge University Press}, address = {Cambridge}, issn = {0007-1145}, doi = {10.1017/S0007114519002538}, pages = {198 -- 208}, year = {2019}, abstract = {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.}, language = {en} } @article{McNultyGoupilAlbaradoetal.2020, author = {McNulty, Margaret A. and Goupil, Brad A. and Albarado, Diana C. and Casta{\~n}o-Martinez, Teresa and Ambrosi, Thomas H. and Puh, Spela and Schulz, Tim Julius and Sch{\"u}rmann, Annette and Morrison, Christopher D. and Laeger, Thomas}, title = {FGF21, not GCN2, influences bone morphology due to dietary protein restrictions}, series = {Bone Reports}, volume = {12}, journal = {Bone Reports}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2352-1872}, doi = {10.1016/j.bonr.2019.100241}, pages = {1 -- 10}, year = {2020}, abstract = {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.}, language = {en} } @article{NaserKadowSchumacheretal.2021, author = {Naser, Eyad and Kadow, Stephanie and Schumacher, Fabian and Mohamed, Zainelabdeen H. and Kappe, Christian and Hessler, Gabriele and Pollmeier, Barbara and Kleuser, Burkhard and Arenz, Christoph and Becker, Katrin Anne and Gulbins, Erich and Carpinteiro, Alexander}, title = {Characterization of the small molecule ARC39}, series = {Journal of Lipid Research}, volume = {61}, journal = {Journal of Lipid Research}, number = {6}, publisher = {American Society for Biochemistry and Molecular Biology}, address = {Bethesda}, issn = {1539-7262}, doi = {10.1194/jlr.RA120000682}, pages = {896 -- 910}, year = {2021}, abstract = {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.}, language = {en} } @article{WeberKochlikDemuthetal.2020, author = {Weber, Daniela and Kochlik, Bastian Max and Demuth, Ilja and Steinhagen-Thiessen, Elisabeth and Grune, Tilman and Norman, Kristina}, title = {Plasma carotenoids, tocopherols and retinol}, series = {Redox Biology}, volume = {32}, journal = {Redox Biology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2213-2317}, doi = {10.1016/j.redox.2020.101461}, pages = {1 -- 8}, year = {2020}, abstract = {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.}, language = {en} } @article{OlayideLargeStridhetal.2020, author = {Olayide, Priscilla and Large, Annabel and Stridh, Linnea and Rabbi, Ismail and Baldermann, Susanne and Stavolone, Livia and Alexandersson, Erik}, title = {Gene expression and metabolite profiling of thirteen Nigerian cassava landraces to elucidate starch and carotenoid composition}, series = {Agronomy}, volume = {10}, journal = {Agronomy}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {2073-4395}, doi = {10.3390/agronomy10030424}, pages = {1 -- 16}, year = {2020}, abstract = {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.}, language = {en} } @article{KesslerHornemannRudovichetal.2020, author = {Kessler, Katharina and Hornemann, Silke and Rudovich, Natalia and Weber, Daniela and Grune, Tilman and Kramer, Achim and Pfeiffer, Andreas F. H. and Pivovarova-Ramich, Olga}, title = {Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers}, series = {Nutrients}, journal = {Nutrients}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu12020340}, pages = {1 -- 12}, year = {2020}, abstract = {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.}, language = {en} } @inproceedings{SchenkeSchjeidePuescheletal.2020, author = {Schenke, Maren and Schjeide, Brit-Maren and P{\"u}schel, Gerhard and Seeger, Bettina}, title = {Human motor neurons diffentiated from plutipotent stem cells as superior traged cells for botulinum neuotoxin potency testing}, series = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {393}, booktitle = {Naunyn-Schmiedeberg's archives of pharmacology}, number = {SUPPL 1}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {0028-1298}, doi = {10.1007/s00210-020-01828-y}, pages = {10 -- 10}, year = {2020}, language = {en} } @article{FinkSchumacherSchlegeletal.2021, author = {Fink, Julian and Schumacher, Fabian and Schlegel, Jan and Stenzel, Philipp and Wigger, Dominik and Sauer, Markus and Kleuser, Burkhard and Seibel, J{\"u}rgen}, title = {Azidosphinganine enables metabolic labeling and detection of sphingolipid de novo synthesis}, series = {Organic \& biomolecular chemistry : an international journal of synthetic, physical and biomolecular organic chemistry}, volume = {19}, journal = {Organic \& biomolecular chemistry : an international journal of synthetic, physical and biomolecular organic chemistry}, number = {10}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1477-0520}, doi = {10.1039/d0ob02592e}, pages = {2203 -- 2212}, year = {2021}, abstract = {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.}, language = {en} } @article{BishopMachateHenningetal.2022, author = {Bishop, Christopher Allen and Machate, Tina and Henning, Thorsten and Henkel-Oberl{\"a}nder, Janin and P{\"u}schel, Gerhard and Weber, Daniela and Grune, Tilman and Klaus, Susanne and Weitkunat, Karolin}, title = {Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle}, series = {Nutrition \& Diabetes}, volume = {12}, journal = {Nutrition \& Diabetes}, number = {1}, publisher = {Nature Publishing Group}, address = {London}, issn = {2044-4052}, doi = {10.1038/s41387-022-00200-8}, pages = {9}, year = {2022}, abstract = {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.}, language = {en} } @article{NicolaiWittFrieseetal.2022, author = {Nicolai, Merle Marie and Witt, Barbara and Friese, Sharleen and Michaelis, Vivien and H{\"o}lz-Armstrong, Lisa and Martin, Maximilian and Ebert, Franziska and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Mechanistic studies on the adverse effects of manganese overexposure in differentiated LUHMES cells}, series = {Food and chemical toxicology}, volume = {161}, journal = {Food and chemical toxicology}, publisher = {Elsevier}, address = {Oxford}, issn = {0278-6915}, doi = {10.1016/j.fct.2022.112822}, pages = {10}, year = {2022}, abstract = {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.}, language = {en} } @article{KlausIgualGilOst2021, author = {Klaus, Susanne and Igual Gil, Carla and Ost, Mario}, title = {Regulation of diurnal energy balance by mitokines}, series = {Cellular and molecular life sciences : CMLS}, volume = {78}, journal = {Cellular and molecular life sciences : CMLS}, number = {7}, publisher = {Springer International Publishing AG}, address = {Cham (ZG)}, issn = {1420-682X}, doi = {10.1007/s00018-020-03748-9}, pages = {3369 -- 3384}, year = {2021}, abstract = {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.}, language = {en} } @article{BurkhardtRauschKlopfleischetal.2021, author = {Burkhardt, Wiebke and Rausch, Theresa and Klopfleisch, Robert and Blaut, Michael and Braune, Annett}, title = {Impact of dietary sulfolipid-derived sulfoquinovose on gut microbiota composition and inflammatory status of colitis-prone interleukin-10-deficient mice}, series = {International journal of medical microbiology : IJMM}, volume = {311}, journal = {International journal of medical microbiology : IJMM}, number = {3}, publisher = {Elsevier}, address = {M{\"u}nchen}, issn = {1618-0607}, doi = {10.1016/j.ijmm.2021.151494}, pages = {11}, year = {2021}, abstract = {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.}, language = {en} } @misc{RodriguezSillkeSchumannLissneretal.2020, author = {Rodr{\´i}guez Sillke, Yasmina and Schumann, Michael and Lissner, Donata and Branchi, Frederica and Glauben, Rainer and Siegmund, Britta}, title = {Small intestinal inflammation but not colitis drives pro-inflammatory nutritional antigen-specific T-cell response}, series = {Journal of Crohn's and Colitis}, volume = {14}, journal = {Journal of Crohn's and Colitis}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1873-9946}, doi = {10.1093/ecco-jcc/jjz203.172}, pages = {S154 -- S155}, year = {2020}, abstract = {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.}, language = {en} } @article{VolkBrandschSchlegelmilchetal.2020, author = {Volk, Christin and Brandsch, Corinna and Schlegelmilch, Ulf and Wensch-Dorendorf, Monika and Hirche, Frank and Simm, Andreas and Gargum, Osama and Wiacek, Claudia and Braun, Peggy G. and Kopp, Johannes F. and Schwerdtle, Tanja and Treede, Hendrik and Stangl, Gabriele I.}, title = {Postprandial metabolic response to rapeseed protein in healthy subjects}, series = {Nutrients}, volume = {12}, journal = {Nutrients}, number = {8}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu12082270}, pages = {22}, year = {2020}, abstract = {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.}, language = {en} } @article{Schulze2021, author = {Schulze, Matthias Bernd}, title = {Dietary linoleic acid: will modifying dietary fat quality reduce the risk of type 2 diabetes?}, series = {Diabetes care}, volume = {44}, journal = {Diabetes care}, number = {9}, publisher = {American Diabetes Association}, address = {Alexandria}, issn = {0149-5992}, doi = {10.2337/dci21-0031}, pages = {1913 -- 1915}, year = {2021}, language = {en} } @inproceedings{SchenkeSchjeidePuescheletal.2021, author = {Schenke, Maren and Schjeide, Brit-Maren and P{\"u}schel, Gerhard Paul and Seeger, Bettina}, title = {Serotype-specific sensitivity to Botulinum neurotoxins of iPSC-derived motor neurons}, series = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {394}, booktitle = {Naunyn-Schmiedeberg's archives of pharmacology}, number = {Suppl. 1}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {0028-1298}, doi = {10.1007/s00210-021-02066-6}, pages = {S4 -- S4}, year = {2021}, language = {en} } @article{JannaschNickelBergmannetal.2022, author = {Jannasch, Franziska and Nickel, Daniela V. and Bergmann, Manuela M. and Schulze, Matthias Bernd}, title = {A new evidence-based diet score to capture associations of food consumption and chronic disease risk}, series = {Nutrients / Molecular Diversity Preservation International (MDPI)}, volume = {14}, journal = {Nutrients / Molecular Diversity Preservation International (MDPI)}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu14112359}, pages = {16}, year = {2022}, abstract = {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.}, language = {en} }