TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

• Published in: Cell research 2012-03, Vol.22 (3), p.551-564
• Main Authors: Luo, Zhidan, Ma, Liqun, Zhao, Zhigang, He, Hongbo, Yang, Dachun, Feng, Xiaoli, Ma, Shuangtao, Chen, Xiaoping, Zhu, Tianqi, Cao, Tingbing, Liu, Daoyan, Nilius, Bernd, Huang, Yu, Yan, Zhencheng, Zhu, Zhiming
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Cell Biology; Cells, Cultured; Energy Metabolism; Life Sciences; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Original; original-article; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PGC-1; Physical Conditioning, Animal - physiology; Physical Endurance - physiology; Trans-Activators - metabolism; Transcription Factors; TRPV Cation Channels - deficiency; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Up-Regulation; 小鼠; 激活; 能量代谢; 辣椒素受体; 过氧化物酶体; 运动耐力; 骨髓细胞
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2011.205

Impaired aerobic exercise capacity and skeletal muscle dysfunction are associated with cardiometabolic diseases. Acute administration of capsaicin enhances exercise endurance in rodents, but the long-term effect of dietary capsaicin is unknown. The capsaicin receptor, the transient receptor potential vaniUoid 1 （TRPV1） cation channel has been detected in skeletal muscle, the role of which remains unclear. Here we report the function of TRPV1 in cultured C2C12 myocytes and the effect of TRPV1 activation by dietary capsaicin on energy metabolism and exercise endurance of skeletal muscles in mice. In vitro, capsaicin increased cytosolic free calcium and peroxisome proliferator-acti- vated receptor-γcoactivator-1α （PGC-1α） expression in C2C12 myotubes through activating TRPV1. In vivo, PGC-1α in skeletal muscle was upregulated by capsaicin-induced TRPV1 activation or genetic overexpression of TRPV1 in mice. TRPV1 activation increased the expression of genes involved in fatty acid oxidation and mitochondrial respiration, promoted mitochondrial biogenesis, increased oxidative fbers, enhanced exercise endurance and prevented high-fat diet-induced metabolic disorders. Importantly, these effects of capsaicin were absent in TRPVl-deficient mice. We conclude that TRPV1 activation by dietary capsaicin improves energy metabolism and exercise endurance by upregulating PGC-1α in skeletal muscles. The present results indicate a novel therapeutic strategy for managing metabolic diseases and improving exercise endurance.