Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway

Yuan,Yexian; Xu,Yaqiong; Xu,Jingren; Liang,Bingqing; Cai,Xingcai; Zhu,Canjun; Wang,Lina; Wang,Songbo; Zhu,Xiaotong; Gao,Ping; Wang,Xiuqi; Zhang,Yongliang; Jiang,Qingyan; Shu,Gang

doi:10.3892/mmr.2017.7554

Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway

Authors:
- Yexian Yuan
- Yaqiong Xu
- Jingren Xu
- Bingqing Liang
- Xingcai Cai
- Canjun Zhu
- Lina Wang
- Songbo Wang
- Xiaotong Zhu
- Ping Gao
- Xiuqi Wang
- Yongliang Zhang
- Qingyan Jiang
- Gang Shu
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Affiliations: Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong 510642, P.R. China
Published online on: September 20, 2017 https://doi.org/10.3892/mmr.2017.7554
Pages: 7361-7366
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It is well known that endurance training is effective to attenuate skeletal muscle atrophy. Succinate is a typical TCA metabolite, of which exercise could dramatically increase the content. The present study aimed to investigate the effect of succinate on protein synthesis in skeletal muscle, and try to delineate the underlying mechanism. The in vitro study revealed that succinate dose‑dependently increased protein synthesis in C2C12 myotube along with the enhancement of phosphorylation levels of AKT Serine/Threonine Kinase 1(Akt), mammalian target of rapamycin, S6, eukaryotic translation initiation factor 4E, 4E binding protein 1 and forkhead box O (FoxO) 3a. Furthermore, it was demonstrated that 20 mM succinate markedly increased [Ca2+]i. Then, the phospho‑extracellular regulated kinase (Erk), ‑Akt level and the crosstalk between Erk and Akt were elevated in response to succinate. Notably, the Erk antagonist (U0126) or mTOR inhibitor (rapamycin) abolished the effect of succinate on protein synthesis. The in vivo study verified that succinate dose‑dependently increased the protein synthesis, in addition to phosphorylation levels of Erk, Akt and FoxO3a in gastrocnemius muscle. In summary, these findings demonstrated that succinate promoted skeletal muscle protein deposition via Erk/Akt signaling pathway.

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