Premium
Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation
Author(s) -
Yuan Yexian,
Xu Pingwen,
Jiang Qingyan,
Cai Xingcai,
Wang Tao,
Peng Wentong,
Sun Jiajie,
Zhu Canjun,
Zhang Cha,
Yue Dong,
He Zhihui,
Yang Jinping,
Zeng Yuxian,
Du Man,
Zhang Fenglin,
Ibrahimi Lucas,
Schaul Sarah,
Jiang Yuwei,
Wang Jiqiu,
Sun Jia,
Wang Qiaoping,
Liu Liming,
Wang Songbo,
Wang Lina,
Zhu Xiaotong,
Gao Ping,
Xi Qianyun,
Yin Cong,
Li Fan,
Xu Guli,
Zhang Yongliang,
Shu Gang
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019103304
Subject(s) - china , agriculture , research center , biology , agricultural economics , agricultural science , library science , microbiology and biotechnology , political science , ecology , computer science , law , economics
Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here, we identified a myometabolite‐mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in mice. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate α‐ketoglutaric acid ( AKG ) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI . Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue ( BAT ) thermogenesis, and white adipose tissue ( WAT ) lipolysis in vivo . We further found that AKG stimulates the adrenal release of adrenaline through 2‐oxoglutarate receptor 1 ( OXGR 1) expressed in adrenal glands. Finally, by using both loss‐of‐function and gain‐of‐function mouse models, we showed that OXGR 1 is essential for AKG ‐mediated exercise‐induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.