@article{GanchevaOuniJeleniketal.2019, author = {Gancheva, Sofiya and Ouni, Meriem and Jelenik, Tomas and Koliaki, Chrysi and Szendroedi, Julia and Toledo, Frederico G. S. and Markgraf, Daniel Frank and Pesta, Dominik H. and Mastrototaro, Lucia and De Filippo, Elisabetta and Herder, Christian and J{\"a}hnert, Markus and Weiss, J{\"u}rgen and Strassburger, Klaus and Schlensak, Matthias and Sch{\"u}rmann, Annette and Roden, Michael}, title = {Dynamic changes of muscle insulin sensitivity after metabolic surgery}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, publisher = {Nature Publ. Group}, address = {London}, issn = {2041-1723}, doi = {10.1038/s41467-019-12081-0}, pages = {13}, year = {2019}, abstract = {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.}, language = {en} } @article{SaussenthalerOuniBaumeieretal.2019, author = {Saussenthaler, Sophie and Ouni, Meriem and Baumeier, Christian and Schwerbel, Kristin and Gottmann, Pascal and Christmann, Sabrina and Laeger, Thomas and Sch{\"u}rmann, Annette}, title = {Epigenetic regulation of hepatic Dpp4 expression in response to dietary protein}, series = {The journal of nutritional biochemistry}, volume = {63}, journal = {The journal of nutritional biochemistry}, publisher = {Elsevier}, address = {New York}, issn = {0955-2863}, doi = {10.1016/j.jnutbio.2018.09.025}, pages = {109 -- 116}, year = {2019}, abstract = {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.}, language = {en} } @article{OuniSchuermann2020, author = {Ouni, Meriem and Sch{\"u}rmann, Annette}, title = {Epigenetic contribution to obesity}, series = {Mammalian genome}, volume = {31}, journal = {Mammalian genome}, number = {5-6}, publisher = {Springer}, address = {New York, NY ; Berlin ; Heidelberg [u.a.]}, issn = {0938-8990}, doi = {10.1007/s00335-020-09835-3}, pages = {134 -- 145}, year = {2020}, abstract = {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.}, language = {en} } @article{WittenbecherOuniKuxhausetal.2019, author = {Wittenbecher, Clemens and Ouni, Meriem and Kuxhaus, Olga and J{\"a}hnert, Markus and Gottmann, Pascal and Teichmann, Andrea and Meidtner, Karina and Kriebel, Jennifer and Grallert, Harald and Pischon, Tobias and Boeing, Heiner and Schulze, Matthias Bernd and Sch{\"u}rmann, Annette}, title = {Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes}, series = {Diabetes : a journal of the American Diabetes Association}, volume = {68}, journal = {Diabetes : a journal of the American Diabetes Association}, number = {1}, publisher = {American Diabetes Association}, address = {Alexandria}, issn = {0012-1797}, doi = {10.2337/db18-0620}, pages = {188 -- 197}, year = {2019}, abstract = {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.}, language = {en} }