@misc{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 = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, issn = {1866-8372}, doi = {10.25932/publishup-51629}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-516297}, pages = {12}, 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{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} } @misc{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 = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {6}, issn = {1866-8372}, doi = {10.25932/publishup-51663}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-516635}, pages = {17}, 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{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} } @misc{WeberKochlikDemuthetal.2020, author = {Weber, Daniela and Kochlik, Bastian and Demuth, Ilja and Steinhagen-Thiessen, Elisabeth and Grune, Tilman and Norman, Kristina}, title = {Plasma carotenoids, tocopherols and retinol}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, issn = {1866-8372}, doi = {10.25932/publishup-51599}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-515996}, pages = {10}, 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{WeberKochlikDemuthetal.2020, author = {Weber, Daniela and Kochlik, Bastian 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} } @misc{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 = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {3}, issn = {1866-8372}, doi = {10.25932/publishup-51783}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-517834}, pages = {18}, 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{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} } @misc{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 = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {2}, issn = {1866-8372}, doi = {10.25932/publishup-51207}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-512079}, pages = {14}, 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} } @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} } @misc{SchedlbauerBlaueRailaetal.2020, author = {Schedlbauer, Carola and Blaue, Dominique and Raila, Jens and Vervuert, Ingrid}, title = {Alterations of serum vitamin E and vitamin A concentrations of ponies and horses during experimentally induced obesity}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {5}, issn = {1866-8372}, doi = {10.25932/publishup-51951}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-519515}, pages = {10}, year = {2020}, abstract = {Vitamin A, vitamin E and retinol-binding protein 4 (RBP4) are a focus of current obesity research in humans. The impact of body weight (BW) gain on fat-soluble vitamins and its associated parameters in equines has not been previously reported. Ten Shetland ponies and 9 Warmblood horses, all adult geldings, non-obese and healthy, were fed an excessive energy diet for 20 months to induce BW gain. Serum alpha-tocopherol (vitamin E), retinol (vitamin A), retinol-binding protein 4 (RBP4) and retinol/RBP4 ratio were analysed before BW gain induction and at six timepoints during the BW gaining period. The mean (+/- SD) \% BW gain achieved during two years of excess energy intake was 29.9 +/- 19.4\% for ponies and 17 +/- 6.74\% for horses. Serum alpha-tocopherol increased significantly in ponies and horses during excess energy intake and circulating alpha-tocopherol levels correlated positively with alpha-tocopherol intake (r = .6; p < .001). Serum retinol concentrations showed variations during the study but without relation to intake. Serum RBP4 decreased at the end of the study. The retinol/RBP4 ratio increased with BW gain without differences between ponies and horses. In comparison with human research, the increase in the retinol/RBP4 ratio was unexpected and needs further elucidation.}, 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{Schweigert2024, author = {Schweigert, Florian J.}, title = {H{\"a}sslich aber gut}, series = {Du sollst nicht essen: Warum Menschen auf Nahrung verzichten - interdisziplin{\"a}re Zug{\"a}nge}, journal = {Du sollst nicht essen: Warum Menschen auf Nahrung verzichten - interdisziplin{\"a}re Zug{\"a}nge}, editor = {Kollodzeiski, Ulrike and Hafner, Johann Evangelist}, publisher = {Ergon Verlag}, address = {Baden-Baden}, isbn = {978-3-98740-007-0}, doi = {10.5771/9783987400087}, pages = {47 -- 59}, year = {2024}, language = {de} } @misc{KollodzeiskiHafnerLippertetal.2024, author = {Kollodzeiski, Ulrike and Hafner, Johann Evangelist and Lippert, Rachel N. and Bartelmeß, Tina and Schweigert, Florian J. and Bigalke, Bernadett and Krochmalnik, Daniel and Sanc{\i}, Kadir and Kardas, Arhan and Dietzel, Irene and Yilmaz, R{\"u}meysa and Olhoeft, Netanel and Struß, Lukas}, title = {Du sollst nicht essen}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Philosophische Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Philosophische Reihe}, number = {191}, editor = {Kollodzeiski, Ulrike and Hafner, Johann Evangelist}, issn = {1866-8380}, doi = {10.25932/publishup-62754}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-627542}, year = {2024}, abstract = {Zwar sind Menschen biologisch gesehen Allesesser, dennoch gibt es keine Gemeinschaft, die alle ihr zur Verf{\"u}gung stehenden Nahrungsmittel voll aussch{\"o}pft. Immer wird etwas nicht gegessen. Warum wir nicht essen, was wir nicht essen - das beleuchtet dieser Sammelband aus neuro-, ern{\"a}hrungs-, gesellschafts- und religionswissenschaftlicher Perspektive. Ein „religi{\"o}ser Nutriscore" gibt Auskunft {\"u}ber die wichtigsten Verzichtsregeln in Judentum, Christentum und Islam. Eine Fotostrecke veranschaulicht, wie bestimmte Speisen zu Festen und Feiertagen zu einem heiligen Essen werden. Nicht zuletzt werden Wege aufgezeigt, wie Menschen, die verschiedene Speiseregeln befolgen, dennoch zusammen essen k{\"o}nnen - inklusive Praxistest in der Unimensa.}, language = {de} } @book{KollodzeiskiHafnerLippertetal.2024, author = {Kollodzeiski, Ulrike and Hafner, Johann Evangelist and Lippert, Rachel N. and Bartelmeß, Tina and Schweigert, Florian J. and Bigalke, Bernadett and Krochmalnik, Daniel and Sanc{\i}, Kadir and Kardas, Arhan and Dietzel, Irene and Yilmaz, R{\"u}meysa and Olhoeft, Netanel and Struß, Lukas}, title = {Du sollst nicht essen}, editor = {Kollodzeiski, Ulrike and Hafner, Johann Evangelist}, publisher = {Ergon Verlag}, address = {Baden-Baden}, isbn = {978-3-98740-007-0}, doi = {10.5771/9783987400087}, year = {2024}, abstract = {Zwar sind Menschen biologisch gesehen Allesesser, dennoch gibt es keine Gemeinschaft, die alle ihr zur Verf{\"u}gung stehenden Nahrungsmittel voll aussch{\"o}pft. Immer wird etwas nicht gegessen. Warum wir nicht essen, was wir nicht essen - das beleuchtet dieser Sammelband aus neuro-, ern{\"a}hrungs-, gesellschafts- und religionswissenschaftlicher Perspektive. Ein „religi{\"o}ser Nutriscore" gibt Auskunft {\"u}ber die wichtigsten Verzichtsregeln in Judentum, Christentum und Islam. Eine Fotostrecke veranschaulicht, wie bestimmte Speisen zu Festen und Feiertagen zu einem heiligen Essen werden. Nicht zuletzt werden Wege aufgezeigt, wie Menschen, die verschiedene Speiseregeln befolgen, dennoch zusammen essen k{\"o}nnen - inklusive Praxistest in der Unimensa.}, language = {de} } @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} }