TY - JOUR A1 - Gancheva, Sofiya A1 - Ouni, Meriem A1 - Jelenik, Tomas A1 - Koliaki, Chrysi A1 - Szendroedi, Julia A1 - Toledo, Frederico G. S. A1 - Markgraf, Daniel Frank A1 - Pesta, Dominik H. A1 - Mastrototaro, Lucia A1 - De Filippo, Elisabetta A1 - Herder, Christian A1 - Jähnert, Markus A1 - Weiss, Jürgen A1 - Strassburger, Klaus A1 - Schlensak, Matthias A1 - Schürmann, Annette A1 - Roden, Michael T1 - Dynamic changes of muscle insulin sensitivity after metabolic surgery JF - Nature Communications N2 - The mechanisms underlying improved insulin sensitivity after surgically-induced weight loss are still unclear. We monitored skeletal muscle metabolism in obese individuals before and over 52 weeks after metabolic surgery. Initial weight loss occurs in parallel with a decrease in muscle oxidative capacity and respiratory control ratio. Persistent elevation of intramyocellular lipid intermediates, likely resulting from unrestrained adipose tissue lipolysis, accompanies the lack of rapid changes in insulin sensitivity. Simultaneously, alterations in skeletal muscle expression of genes involved in calcium/lipid metabolism and mitochondrial function associate with subsequent distinct DNA methylation patterns at 52 weeks after surgery. Thus, initial unfavorable metabolic changes including insulin resistance of adipose tissue and skeletal muscle precede epigenetic modifications of genes involved in muscle energy metabolism and the long-term improvement of insulin sensitivity. Y1 - 2019 U6 - https://doi.org/10.1038/s41467-019-12081-0 SN - 2041-1723 VL - 10 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Saussenthaler, Sophie A1 - Ouni, Meriem A1 - Baumeier, Christian A1 - Schwerbel, Kristin A1 - Gottmann, Pascal A1 - Christmann, Sabrina A1 - Laeger, Thomas A1 - Schürmann, Annette T1 - Epigenetic regulation of hepatic Dpp4 expression in response to dietary protein JF - The journal of nutritional biochemistry N2 - Dipeptidyl peptidase 4 (DPP4) is known to be elevated in metabolic disturbances such as obesity, type 2 diabetes and fatty liver disease. Lowering DPP4 concentration by pharmacological inhibition improves glucose homeostasis and exhibits beneficial effects to reduce hepatic fat content. As factors regulating the endogenous expression of Dpp4 are unknown, the aim of this study was to examine whether the Dpp4 expression is epigenetically regulated in response to dietary components. Primary hepatocytes were treated with different macronutrients, and Dpp4 mRNA levels and DPP4 activity were evaluated. Moreover, dietary low-protein intervention was conducted in New Zealand obese (NZO) mice, and subsequently, effects on Dpp4 expression, methylation as well as plasma concentration and activity were determined. Our results indicate that Dpp4 mRNA expression is mediated by DNA methylation in several tissues. We therefore consider the Dpp4 southern shore as tissue differentially methylated region. Amino acids increased Dpp4 expression in primary hepatocytes, whereas glucose and fatty acids were without effect. Dietary protein restriction in NZO mice increased Dpp4 DNA methylation in liver leading to diminished Dpp4 expression and consequently to lowered plasma DPP4 activity. We conclude that protein restriction in the adolescent and adult states is a sufficient strategy to reduce DPP4 which in turn contributes to improve glucose homeostasis. (C) 2018 Published by Elsevier Inc. KW - DPP4 KW - DNA methylation KW - Protein restriction KW - Type 2 diabetes KW - NZO Y1 - 2019 U6 - https://doi.org/10.1016/j.jnutbio.2018.09.025 SN - 0955-2863 SN - 1873-4847 VL - 63 SP - 109 EP - 116 PB - Elsevier CY - New York ER - TY - JOUR A1 - Ouni, Meriem A1 - Schürmann, Annette T1 - Epigenetic contribution to obesity JF - Mammalian genome N2 - Obesity is a worldwide epidemic and contributes to global morbidity and mortality mediated via the development of nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), cardiovascular (CVD) and other diseases. It is a consequence of an elevated caloric intake, a sedentary lifestyle and a genetic as well as an epigenetic predisposition. This review summarizes changes in DNA methylation and microRNAs identified in blood cells and different tissues in obese human and rodent models. It includes information on epigenetic alterations which occur in response to fat-enriched diets, exercise and metabolic surgery and discusses the potential of interventions to reverse epigenetic modifications. Y1 - 2020 U6 - https://doi.org/10.1007/s00335-020-09835-3 SN - 0938-8990 SN - 1432-1777 VL - 31 IS - 5-6 SP - 134 EP - 145 PB - Springer CY - New York, NY ; Berlin ; Heidelberg [u.a.] ER - TY - JOUR A1 - Wittenbecher, Clemens A1 - Ouni, Meriem A1 - Kuxhaus, Olga A1 - Jähnert, Markus A1 - Gottmann, Pascal A1 - Teichmann, Andrea A1 - Meidtner, Karina A1 - Kriebel, Jennifer A1 - Grallert, Harald A1 - Pischon, Tobias A1 - Boeing, Heiner A1 - Schulze, Matthias Bernd A1 - Schürmann, Annette T1 - Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes JF - Diabetes : a journal of the American Diabetes Association N2 - Recent studies suggest that insulin-like growth factor binding protein 2 (IGFBP-2) may protect against type 2 diabetes, but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the IGFBP-2 gene with type 2 diabetes risk. Y1 - 2019 U6 - https://doi.org/10.2337/db18-0620 SN - 0012-1797 SN - 1939-327X VL - 68 IS - 1 SP - 188 EP - 197 PB - American Diabetes Association CY - Alexandria ER -