Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures

Cell Genom. 2024 Jun 12;4(6):100421. doi: 10.1016/j.xgen.2023.100421. Epub 2024 May 1.


Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.

Keywords: ATAC-seq; DNA methylation; GPCR; RNA-seq; RRBS; chromatin accessibility; endurance training; sex differences; tissue specificity; transcriptome.

MeSH terms

  • Adaptation, Physiological / genetics
  • Animals
  • DNA Methylation
  • Epigenesis, Genetic
  • Epigenomics
  • Female
  • Male
  • Organ Specificity
  • Physical Conditioning, Animal* / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Transcriptome*