Protective effect of 5-heptadecylresorcinol against obesity-associated skeletal muscle dysfunction by modulating mitochondrial biogenesis via the activation of SIRT3/PGC-1α signaling pathway

[Display omitted] •5-heptadecylresorcinol (AR-C17) improves muscle dysfunction.•AR-C17 enhances mitochondrial content and mitochondrial biosynthesis.•AR-C17 improves obesity-induced muscle dysfunction via modulation of SIRT3/PGC-1α signaling pathway.•AR-C17 can be used as functional food ingredient to regulate obesity-associated muscle metabolic diseases. Obesity-associated skeletal muscle mitochondrial dysfunction contributed to exercise capacity decline. 5-heptadecylresorcinol (AR-C17) has been proven effective against obesity and insulin resistance. However, its effects on skeletal muscle performance remains unclear. In this study, we investigate whether AR-C17 could protect against high-fat diet induced C57 BL/6J mice skeletal muscle dysfunction. The results indicated that AR-C17 intervention significantly improved skeletal muscle exercise capacity according to the strength and endurance test. AR-C17 showed no effect on skeletal muscle myofiber type conversion and myogenesis, but could significantly enhance PGC-1α mediated mitochondrial biogenesis. Moreover, AR-C17 significantly attenuated PA-induced reduction of mitochondrial DNA content in C2C12 cells and promoted mitochondrial biogenesis regulator gene PGC-1α and its downstream signaling pathway protein expression. In addition, AR-C17 increased the protein levels of SIRT3, while the protective effect was abolished by SIRT3 inhibitor (3-TYP), indicating AR-C17 ameliorated obesity induced skeletal muscle dysfunction might through SIRT3/PGC-1α signaling pathway.