Lifestyle induced adaptations of the skeletal muscle transcriptome and methylome

Objective Lifestyle interventions can protect against skeletal muscle (SM) insulin resistance and an increasing number of studies suggests that epigenetic changes might be responsible for these beneficial effects. Therefore, we aimed to dissect the transcriptomic adaptations of the SM to dietary and exercise-based lifestyle interventions and determine the degree of epigenetic contribution.

Methods Genome-wide RNA-sequencing and DNA-methylation analysis was performed in SM of diabetes susceptible NZO mice after time restricted eating (TRE) or alternate day fasting (ADF) and in healthy C57BL/6J mice subjected to exercise (EX).

Results Interestingly, TRE and ADF triggered mostly independent changes in gene expression. Less than 15% of ADF-responsive genes were regulated by TRE in similar direction (256 genes). In contrast, 30% of ADF-regulated genes were also regulated by exercise, however, 85% of them were regulated in opposite directions (59 genes). Despite low concordance of regulated gene sets, pathway analysis revealed that ADF and EX coincide in processes relevant for muscle mass maintenance, whereas TRE was mainly characterized by nutrient metabolism. In respect to epigenetic alterations we identified only about 10% differentially expressed genes which also showed differences in DNA methylation. We discovered 71 genes, which were commonly regulated after all lifestyle interventions, of which only 3 were consistently epigenetically regulated.

Conclusion The beneficial effects on SM health provided by TRE, ADF and EX are based on divergent molecular adaptations. Epigenetic alterations appear to play a minor role in mediating these expression changes.

Publikationsverlauf

Artikel online veröffentlicht:
02. Mai 2023