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Succinate induces skeletal muscle fiber remodeling via SUCNR1 signaling
Author(s) -
Wang Tao,
Xu YaQiong,
Yuan YeXian,
Xu PingWen,
Zhang Cha,
Li Fan,
Wang LiNa,
Yin Cong,
Zhang Lin,
Cai XingCai,
Zhu CanJun,
Xu JingRen,
Liang BingQing,
Schaul Sarah,
Xie PeiPei,
Yue Dong,
Liao ZhengRui,
Yu LuLu,
Luo Lv,
Zhou Gan,
Yang JinPing,
He ZhiHui,
Du Man,
Zhou YuPing,
Deng BaiChuan,
Wang SongBo,
Gao Ping,
Zhu XiaoTong,
Xi QianYun,
Zhang YongLiang,
Shu Gang,
Jiang QingYan
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201947892
Subject(s) - skeletal muscle , microbiology and biotechnology , chemistry , fiber , signal transduction , biology , anatomy , organic chemistry
The conversion of skeletal muscle fiber from fast twitch to slow‐twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid ( TCA ) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber‐type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain II b expression. Further, by using pharmacological or genetic loss‐of‐function models generated by phospholipase Cβ antagonists, SUCNR1 global knockout, or SUCNR1 gastrocnemius‐specific knockdown, we found that the effects of succinate on skeletal muscle fiber‐type remodeling are mediated by SUCNR1 and its downstream calcium/ NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUCNR1 signaling pathway. These findings suggest the potential beneficial use of succinate‐based compounds in both athletic and sedentary populations.