title: TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice.
abstract: 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 vanilloid 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-activated receptor-γ coactivator-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 fibers, enhanced exercise endurance and prevented high-fat diet-induced metabolic disorders. Importantly, these effects of capsaicin were absent in TRPV1-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.
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Luo
authors.forename: Liqun
authors.initials: L
authors.lastname: Ma
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Feng
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Tianqi
authors.initials: T
authors.lastname: Zhu
authors.forename: Tingbing
authors.initials: T
authors.lastname: Cao
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004734:Energy Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology*; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D015854:Up-Regulation
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors