Effects of a 4-week high-fat diet on transcriptome and DNA methylation after muscle contractions in rat skeletal muscle.

Increase in mRNA expression following muscle contraction regulates exercise-induced cellular responses associated with exercise adaptation. However, effects of a high-fat diet (HFD) on muscle contraction-induced alterations in transcription and DNA methylation remain unclear. Therefore, this study aimed to identify the effects of a 4-week HFD on transcriptomic responses to muscle contractions and to examine the association between these transcriptomic changes and DNA methylation in promoter regions. Rats were fed either an HFD or a normal diet (ND) for 4 weeks and underwent electrical stimulation-induced muscle contractions (5 sets × 10 contractions of 3 s at 100 Hz) in the right tibialis anterior (TA) muscle. Both TA muscles were harvested 3 h after muscle contractions for transcriptome and DNA methylation analyses. HFD suppressed the expression of 36 genes, and phosphoproteins were enriched as Gene Ontology (GO) terms that are normally upregulated in response to muscle contractions. Furthermore, the expression of 147 genes, myosin heavy chain II, and extracellular matrix were enriched as GO terms and decreased after muscle contractions under HFD conditions, whereas their expression remained unchanged under ND conditions. However, genes whose contraction-induced mRNA expression was altered by HFD were not affected and demonstrated no significant inverse correlation between mRNA expression and DNA methylation levels. Collectively, these results indicate that a 4-week HFD alters the transcriptomic response of specific GOs associated with muscle contractions, whereas these transcriptomic changes were not accompanied by detectable changes in DNA methylation, at least within the regions captured and analyzed in this study.