Integrative profiling of transcriptome and metabolome of skeletal muscle after endurance exercise in a high-fat diet

Objective Regular exercise reduces the risk of obesity, but the impact of endurance exercise on skeletal muscle metabolic processes remains incompletely understood. This study investigated the effects of endurance exercise on the transcriptome and metabolome of skeletal muscle in obese mice. Method Transcriptomic and metabolomic profiling of skeletal muscle samples was performed across experimental groups to identify differentially expressed genes and differential metabolites. Functional enrichment of DEGs and metabolites was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Integrated pathway-level analysis was conducted using iPath 3.0. Results Integrated transcriptomic and metabolomic analysis indicated that endurance exercise altered lipid metabolism, amino acid metabolism, and nucleotide metabolism pathways in the skeletal muscle of obese mice. Specifically, endurance exercise downregulated the expression of lipid metabolism-related gene Acot2 , amino acid metabolism-related gene Nos2 , and carbohydrate metabolism-related genes Itpkb and Inpp4b . Furthermore, endurance exercise decreased the levels of palmitic acid, arachidonate, phosphatidylcholine, acetylcholine, hypoxanthine, urea, and acetyl-CoA. Conclusions Endurance exercise positively impacts skeletal muscle metabolic health in obese mice through coordinated regulation of multiple metabolic pathways and reduction of specific metabolites