Diabetologie und Stoffwechsel 2024; 19(S 01): S6
DOI: 10.1055/s-0044-1785239
Abstracts | DDG 2024
Freie Vorträge
Freie Vorträge 1: Grundlagenforschung Energiestoffwechsel & Adipositas

Epigenetic impact of lifestyle-interventions on metabolic health

Authors

  • Neele Haacke

    1   Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Genetik der Adipositas, Nuthetal, Germany

  • Jasmin Gaugel

    1   Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Genetik der Adipositas, Nuthetal, Germany

  • Michail Lazaratos

    1   Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Genetik der Adipositas, Nuthetal, Germany

  • Markus Jähnert

    2   Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Experimentelle Diabetologie, Nuthetal, Germany

  • Annette Schürmann

    2   Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Experimentelle Diabetologie, Nuthetal, Germany

  • Heike Vogel

    1   Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Genetik der Adipositas, Nuthetal, Germany
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Objective: Studies have repeatedly demonstrated that restricting caloric intake can markedly improve insulin sensitivity and other key metabolic parameters. Here, our objective was to understand which epigenetic alterations, focusing on DNA methylation and the miRNome, participate in the protective effects on metabolic health in mice predisposed to diabetes.

Methods: Genome-wide transcriptomics, DNA-methylation and miRNA analysis were performed in skeletal muscle (SM) and adipose tissue (WAT) of male diabetes-prone New Zealand Obese (NZO) mice after time-restricted feeding (TRF) or alternate-day fasting (ADF).

Results: The in-depth omics analyses revealed significant epigenetic changes in both SM and WAT following lifestyle-interventions, with a more distinct clustering pattern among the groups in WAT compared to SM. Almost 6,000 genes were differentially expressed between ad libitum-fed mice and ADF and nearly 50% exhibited an altered DNA-methylation pattern, with the majority being hypomethylated. Further investigation of the miRNA expression profiles revealed a marked response in WAT, with 153 differentially expressed miRNAs potentially targeting 2,270 genes exhibiting an altered expression. Interestingly, despite distinct gene expression profiles induced by ADF and TRF, a similar enrichment of metabolic pathways such as MAPK and insulin signaling, was detected in response to both lifestyle-interventions in WAT. These common pathways suggest a similar regulatory framework, which was further analyzed by weighted gene co-expression analysis (WGCNA). This network analysis revealed sets of co-expressed genes, with one comprising 3,102 co-expressed genes, implying a similar regulatory mechanism.

Conclusion: Our integrated analyses revealed that lifestyle interventions induce major changes on gene expression level particularly in adipose tissue via epigenetic alterations resulting in improved insulin sensitivity.


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Publication History

Article published online:
18 April 2024

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