Effects of a 4-wk 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-wk 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 wk 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 phosphoprotein was enriched as a Gene Ontology (GO) term. These genes were normally upregulated in response to muscle contractions. Furthermore, myosin heavy chain II, and extracellular matrix were enriched as GO terms for 147 genes that 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-wk 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.NEW & NOTEWORTHY This study aimed to identify the effects of a 4-wk HFD on transcriptomic responses to muscle contractions and to examine the association between these transcriptomic changes and DNA methylation in promoter regions. A 4-wk HFD altered the transcriptomic response of specific GOs, including phosphoprotein, MHC II, and extracellular matrix, associated with muscle contractions. However, integrative analysis revealed that these mRNA expression changes were not accompanied by detectable DNA methylation within the regions analyzed in this study.