TY - JOUR A1 - Bishop, Christopher Allen A1 - Machate, Tina A1 - Henning, Thorsten A1 - Henkel-Oberländer, Janin A1 - Püschel, Gerhard A1 - Weber, Daniela A1 - Grune, Tilman A1 - Klaus, Susanne A1 - Weitkunat, Karolin T1 - Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle JF - Nutrition & Diabetes N2 - Objective: Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake. Methods: To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes). Results: Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure-likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/ insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling. Conclusion: These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance. Y1 - 2022 U6 - https://doi.org/10.1038/s41387-022-00200-8 SN - 2044-4052 VL - 12 IS - 1 PB - Nature Publishing Group CY - London ER - TY - JOUR A1 - Kehm, Richard A1 - Rückriemen, Jana A1 - Weber, Daniela A1 - Deubel, Stefanie A1 - Grune, Tilman A1 - Höhn, Annika T1 - Endogenous advanced glycation end products in pancreatic islets after short-term carbohydrate intervention in obese, diabetes-prone mice JF - Nutrition & Diabetes N2 - Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-epsilon-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions. Y1 - 2019 U6 - https://doi.org/10.1038/s41387-019-0077-x SN - 2044-4052 VL - 9 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Henkel, Janin A1 - Coleman, Charles Dominic A1 - Schraplau, Anne A1 - Jöhrens, Korinna A1 - Weber, Daniela A1 - Castro, Jose Pedro A1 - Hugo, Martin A1 - Schulz, Tim Julius A1 - Krämer, Stephanie A1 - Schürmann, Annette A1 - Püschel, Gerhard Paul T1 - Induction of Steatohepatitis (NASH) with Insulin Resistance in Wild-type B6 Mice by a Western-type Diet Containing Soybean Oil and Cholesterol JF - Molecular medicine N2 - Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of the metabolic syndrome. Many currently used animal models of NAFLD/NASH lack clinical features of either NASH or metabolic syndrome such as hepatic inflammation and fibrosis (e.g., high-fat diets) or overweight and insulin resistance (e.g., methionine-choline-deficient diets), or they are based on monogenetic defects (e.g., ob/ob mice). In the current study, a Western-type diet containing soybean oil with high n-6-PUFA and 0.75% cholesterol (SOD + Cho) induced steatosis, inflammation and fibrosis accompanied by hepatic lipid peroxidation and oxidative stress in livers of C57BL/6-mice, which in addition showed increased weight gain and insulin resistance, thus displaying a phenotype closely resembling all clinical features of NASH in patients with metabolic syndrome. In striking contrast, a soybean oil-containing Western-type diet without cholesterol (SOD) induced only mild steatosis but not hepatic inflammation, fibrosis, weight gain or insulin resistance. Another high-fat diet, mainly consisting of lard and supplemented with fructose in drinking water (LAD + Fru), resulted in more prominent weight gain, insulin resistance and hepatic steatosis than SOD + Cho, but livers were devoid of inflammation and fibrosis. Although both LAD + Fru-and SOD + Cho-fed animals had high plasma cholesterol, liver cholesterol was elevated only in SOD + Cho animals. Cholesterol induced expression of chemotactic and inflammatory cytokines in cultured Kupffer cells and rendered hepatocytes more susceptible to apoptosis. In summary, dietary cholesterol in the SOD + Cho diet may trigger hepatic inflammation and fibrosis. SOD + Cho-fed animals may be a useful disease model displaying many clinical features of patients with the metabolic syndrome and NASH. KW - Nonalcoholic Steatohepatitis (NASH) KW - Typical Western Diet KW - Nonalcoholic Fatty Liver Disease (NAFLD) KW - Dietary Cholesterol KW - Kupffer Cells Y1 - 2017 U6 - https://doi.org/10.2119/molmed.2016.00203 SN - 1076-1551 SN - 1528-3658 VL - 23 SP - 70 EP - 82 PB - Feinstein Inst. for Medical Research CY - Manhasset ER - TY - JOUR A1 - Castaño Martínez, María Teresa A1 - Schumacher, Fabian A1 - Schumacher, Silke A1 - Kochlik, Bastian A1 - Weber, Daniela A1 - Grune, Tilman A1 - Biemann, Ronald A1 - McCann, Adrian A1 - Abraham, Klaus A1 - Weikert, Cornelia A1 - Kleuse, Burkhard A1 - Schürmann, Annette A1 - Laeger, Thomas T1 - Methionine restriction prevents onset of type 2 diabetes in NZO mice JF - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology N2 - Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.-Castano-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schurmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice. KW - energy expenditure KW - hyperglycemia KW - obesity KW - vegan KW - vegetarian Y1 - 2019 U6 - https://doi.org/10.1096/fj.201900150R SN - 0892-6638 SN - 1530-6860 VL - 33 IS - 6 SP - 7092 EP - 7102 PB - Federation of American Societies for Experimental Biology CY - Bethesda ER - TY - JOUR A1 - Nowotny, Kerstin A1 - Castro, Jose Pedro A1 - Hugo, Martin A1 - Braune, Sabine A1 - Weber, Daniela A1 - Pignitter, Marc A1 - Somoza, Veronika A1 - Bornhorst, Julia A1 - Schwerdtle, Tanja A1 - Grune, Tilman T1 - Oxidants produced by methylglyoxal-modified collagen trigger ER stress and apoptosis in skin fibroblasts JF - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research N2 - Methylglyoxal (MG), a highly reactive dicarbonyl, interacts with proteins to form advanced glycation end products (AGEs). AGEs include a variety of compounds which were shown to have damaging potential and to accumulate in the course of different conditions such as diabetes mellitus and aging. After confirming collagen as a main target for MG modifications in vivo within the extracellular matrix, we show here that MG-collagen disrupts fibroblast redox homeostasis and induces endoplasmic reticulum (ER) stress and apoptosis. In particular, MG-collagen-induced apoptosis is associated with the activation of the PERK-eIF2 alpha pathway and caspase-12. MG-collagen contributes to altered redox homeostasis by directly generating hydrogen peroxide and oxygen-derived free radicals. The induction of ER stress in human fibroblasts was confirmed using collagen extracts isolated from old mice in which MG-derived AGEs were enriched. In conclusion, MG-derived AGEs represent one factor contributing to diminished fibroblast function during aging. KW - Advanced glycation end products KW - Aging KW - Apoptosis KW - Collagen KW - ER stress KW - Methylglyoxal KW - Redox homeostasis Y1 - 2018 U6 - https://doi.org/10.1016/j.freeradbiomed.2018.03.022 SN - 0891-5849 SN - 1873-4596 VL - 120 SP - 102 EP - 113 PB - Elsevier CY - New York ER - TY - GEN A1 - Weber, Daniela A1 - Kochlik, Bastian A1 - Demuth, Ilja A1 - Steinhagen-Thiessen, Elisabeth A1 - Grune, Tilman A1 - Norman, Kristina T1 - Plasma carotenoids, tocopherols and retinol BT - Association with age in the Berlin Aging Study II T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1409 KW - carotenoids KW - tocopherols KW - micronutrients KW - age KW - plasma KW - food frequency questionnaire Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515996 SN - 1866-8372 ER - TY - JOUR A1 - Weber, Daniela A1 - Kochlik, Bastian A1 - Demuth, Ilja A1 - Steinhagen-Thiessen, Elisabeth A1 - Grune, Tilman A1 - Norman, Kristina T1 - Plasma carotenoids, tocopherols and retinol BT - Association with age in the Berlin Aging Study II JF - Redox Biology N2 - Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micro-nutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, alpha-carotene, alpha-tocopherol, beta-cryptoxanthin (only in women), and gamma-tocopherol (only in men). beta-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, alpha-carotene (both inverse), alpha-tocopherol, gamma-tocopherol, and beta-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for beta-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and alpha-carotene concentration in older subjects, bioavailability studies in older participants are necessary. KW - carotenoids KW - tocopherols KW - micronutrients KW - age KW - plasma KW - food frequency questionnaire Y1 - 2020 U6 - https://doi.org/10.1016/j.redox.2020.101461 SN - 2213-2317 VL - 32 SP - 1 EP - 8 PB - Elsevier CY - Amsterdam ER - TY - GEN A1 - Stuetz, Wolfgang A1 - Weber, Daniela A1 - Dollé, Martijn E. T. A1 - Jansen, Eugène A1 - Grubeck-Loebenstein, Beatrix A1 - Fiegl, Simone A1 - Toussaint, Olivier A1 - Bernhardt, Juergen A1 - Gonos, Efstathios S. A1 - Franceschi, Claudio A1 - Sikora, Ewa A1 - Moreno-Villanueva, María A1 - Breusing, Nicolle A1 - Grune, Tilman A1 - Bürkle, Alexander T1 - Plasma carotenoids, tocopherols, and retinol in the age-stratified (35–74 years) general population BT - a cross-sectional study in six European countries T2 - Nutrients N2 - Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/β-carotene and higher β-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene (r = −0.248), α-tocopherol (r = 0.208), α-carotene (r = −0.112), and β-cryptoxanthin (r = 0.125; all p < 0.001). Age was inversely associated with lycopene (−6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m2)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher β-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (−4.8% vs. −3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 449 KW - carotenoids KW - plasma KW - age KW - Europe KW - micronutrient KW - lycopene KW - retinol KW - tocopherols Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-407659 ER - TY - GEN A1 - Kessler, Katharina A1 - Hornemann, Silke A1 - Rudovich, Natalia A1 - Weber, Daniela A1 - Grune, Tilman A1 - Kramer, Achim A1 - Pfeiffer, Andreas F. H. A1 - Pivovarova-Ramich, Olga T1 - Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1425 KW - meal timing KW - saliva KW - circadian clock KW - adiponectin KW - resistin KW - visfatin KW - insulin KW - melatonin KW - cortisol KW - cytokines Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-512079 SN - 1866-8372 IS - 2 ER - TY - JOUR A1 - Kessler, Katharina A1 - Hornemann, Silke A1 - Rudovich, Natalia A1 - Weber, Daniela A1 - Grune, Tilman A1 - Kramer, Achim A1 - Pfeiffer, Andreas F. H. A1 - Pivovarova-Ramich, Olga T1 - Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers JF - Nutrients N2 - Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies. KW - meal timing KW - saliva KW - circadian clock KW - adiponectin KW - resistin KW - visfatin KW - insulin KW - melatonin KW - cortisol KW - cytokines Y1 - 2020 U6 - https://doi.org/10.3390/nu12020340 SN - 2072-6643 IS - 2 SP - 1 EP - 12 PB - MDPI CY - Basel ER -