Alpha-ketoglutarate Promotes Skeletal Muscle Hypertrophy and Protein Synthesis Through Akt/mTOR Signaling Pathways

Overview

Journal Sci Rep

Specialty Science

Date 2016 May 27

PMID 27225984

Citations 26

Authors

Xingcai Cai

Canjun Zhu

Yaqiong Xu

Yuanyuan Jing

Yexian Yuan

Lina Wang

Songbo Wang

Xiaotong Zhu

Ping Gao

Yongliang Zhang

Qingyan Jiang

Gang Shu

Affiliations

Soon will be listed here.

Abstract

Skeletal muscle weight loss is accompanied by small fiber size and low protein content. Alpha-ketoglutarate (AKG) participates in protein and nitrogen metabolism. The effect of AKG on skeletal muscle hypertrophy has not yet been tested, and its underlying mechanism is yet to be determined. In this study, we demonstrated that AKG (2%) increased the gastrocnemius muscle weight and fiber diameter in mice. Our in vitro study also confirmed that AKG dose increased protein synthesis in C2C12 myotubes, which could be effectively blocked by the antagonists of Akt and mTOR. The effects of AKG on skeletal muscle protein synthesis were independent of glutamate, its metabolite. We tested the expression of GPR91 and GPR99. The result demonstrated that C2C12 cells expressed GPR91, which could be upregulated by AKG. GPR91 knockdown abolished the effect of AKG on protein synthesis but failed to inhibit protein degradation. These findings demonstrated that AKG promoted skeletal muscle hypertrophy via Akt/mTOR signaling pathway. In addition, GPR91 might be partially attributed to AKG-induced skeletal muscle protein synthesis.

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