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Learn MoreHigh fat feeding is deleterious for skeletal muscle metabolism, while exercise has well documented beneficial effects for these same metabolic features. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression (by RNA-seq) and DNA methylation (by Reduced Representation Bisulfite Sequencing). HFD markedly induced expression of immune and inflammatory genes which was not attenuated by Ex. In contract, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed significant association between DNA methylation changes and gene expression were glycogen phosphorylase, muscle associated (PYGM), which was epigenetically regulated in both groups, and angiopoiten like 4 (ANGPTL4), which was regulated only following Ex. We conclude that Short-term Ex does not prevent HFD-induced inflammatory response, but provokes a genomic response that may preserve skeletal muscle from atrophy. Epigenetic adaptation provides important mechanistic insight into the gene specific regulation of inflammatory and metabolic processes in human skeletal muscle. SOURCE: Lars,Roed,Ingerslev (ingerslev@sund.ku.dk) - Integrative Physiology Copenhagen University
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