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Kovác, L.* ; Goj, T.* ; Ouni, M.* ; Irmler, M. ; Jähnert, M.* ; Beckers, J. ; Hrabě de Angelis, M. ; Peter, A. ; Moller, A. ; Birkenfeld, A.L. ; Weigert, C. ; Schürmann, A.*

Skeletal muscle gene expression signatures of obese high- and low- responders to endurance exercise training.

J. Clin. Endocrinol. Metab. 109, 1318-1327 (2023)

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CONTEXT: Exercise training is known to improve glucose tolerance and reverse insulin resistance in persons 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. LASSO approach identified several novel candidates (e.g. ZCWPW2, FOXRED1, STK40), which 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Dna Methylation ; Lasso ; Exercise ; Gene Expression ; Obesity ; Responders

ISSN (print) / ISBN 0021-972X

e-ISSN 1945-7197

Journal Journal of Clinical Endocrinology & Metabolism, The

Quellenangaben Volume: 109, Issue: 5, Pages: 1318-1327

Publisher Endocrine Society

Publishing Place Bethesda, Md.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Experimental Genetics (IEG)

Grants German Federal Ministry of Education and Research (BMBF)