Skeletal Muscle Gene Expression Signatures of Obese High and Low Responders to Endurance Exercise Training.

Autor:	Kovac L; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal 14558, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Research Group Molecular and Clinical Life Science of Metabolic Diseases, Faculty of Health Sciences Brandenburg, University of Potsdam, Brandenburg 14469, Germany., Goj T; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen 72076, Germany., Ouni M; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal 14558, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany., Irmler M; Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg 85764, Germany., Jähnert M; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal 14558, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany., Beckers J; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg 85764, Germany.; School of Life Sciences, Chair of Experimental Genetics, Technical University Munich, Freising 85764, Germany., Hrabé De Angelis M; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg 85764, Germany.; School of Life Sciences, Chair of Experimental Genetics, Technical University Munich, Freising 85764, Germany., Peter A; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen 72076, Germany.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen, Tübingen 72076, Germany., Moller A; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen, Tübingen 72076, Germany.; Department of Internal Medicine IV, University Hospital Tübingen, Tübingen 72076, Germany., Birkenfeld AL; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen, Tübingen 72076, Germany.; Department of Internal Medicine IV, University Hospital Tübingen, Tübingen 72076, Germany., Weigert C; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen 72076, Germany.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen, Tübingen 72076, Germany., Schürmann A; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal 14558, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg 85764, Germany.; Institute of Nutritional Science, University of Potsdam, Nuthetal 14558, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Apr 19; Vol. 109 (5), pp. 1318-1327.
DOI:	10.1210/clinem/dgad677
Abstrakt:	Context: Exercise training is known to improve glucose tolerance and reverse insulin resistance in people with obesity. However, some individuals fail to improve or even decline in their clinical traits following exercise intervention. Objective: This study focused on gene expression and DNA methylation signatures in skeletal muscle of low (LRE) and high responders (RES) to 8 weeks of supervised endurance training. Methods: We performed skeletal muscle gene expression and DNA methylation analyses in LRE and RES before and after exercise intervention. Additionally, we applied the least absolute shrinkage and selection operator (LASSO) approach to identify predictive marker genes of exercise outcome. Results: We show that the two groups differ markedly already before the intervention. RES were characterized by lower expression of genes involved in DNA replication and repair, and higher expression of extracellular matrix (ECM) components. The LASSO approach identified several novel candidates (eg, ZCWPW2, FOXRED1, STK40) that have not been previously described in the context of obesity and exercise response. Following the intervention, LRE reacted with expression changes of genes related to inflammation and apoptosis, RES with genes related to mitochondrial function. LRE exhibited significantly higher expression of ECM components compared to RES, suggesting improper remodeling and potential negative effects on insulin sensitivity. Between 45% and 70% of differences in gene expression could be linked to differences in DNA methylation. Conclusion: Together, our data offer an insight into molecular mechanisms underlying differences in response to exercise and provide potential novel markers for the success of intervention. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
Databáze:	MEDLINE
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