MTORC1 Mediates Lysine-Induced Satellite Cell Activation to Promote Skeletal Muscle Growth.

Xiu-Qi Wang,Cheng-Long Jin,Jin-Ling Ye,Chun-Qi Gao,Hui-Chao Yan,Hai-Chang Li,Jinzeng Yang

doi:10.3390/cells8121549

Abstract

As the first limiting amino acid, lysine (Lys) has been thought to promote muscle fiber hypertrophy by increasing protein synthesis. However, the functions of Lys seem far more complex than that. Despite the fact that satellite cells (SCs) play an important role in skeletal muscle growth, the communication between Lys and SCs remains unclear. In this study, we investigated whether SCs participate directly in Lys-induced skeletal muscle growth and whether the mammalian target of rapamycin complex 1 (mTORC1) pathway was activated both in vivo and in vitro to mediate SC functions in response to Lys supplementation. Subsequently, the skeletal muscle growth of piglets was controlled by dietary Lys supplementation. Isobaric tag for relative and absolute quantitation (iTRAQ) analysis showed activated SCs were required for longissimus dorsi muscle growth, and this effect was accompanied by mTORC1 pathway upregulation. Furthermore, SC proliferation was governed by medium Lys concentrations, and the mTORC1 pathway was significantly enhanced in vitro. After verifying that rapamycin inhibits the mTORC1 pathway and suppresses SC proliferation, we conclude that Lys is not only a molecular building block for protein synthesis but also a signal that activates SCs to manipulate muscle growth via the mTORC1 pathway.

Highlights

Lysine (Lys) is the first limiting essential amino acid for mammals consuming a predominantly cereal-based diet [1,2]
To study the mechanism of Lys in governing skeletal muscle growth, it has been reported that the mammalian target of rapamycin complex 1 pathway is activated by Lys in the skeletal muscle of rats [10]
To determine the effects of dietary Lys supplementation on the skeletal muscle growth of weaned piglets, we developed the experimental design shown in Supplemental Table 1

Summary

Introduction

Lysine (Lys) is the first limiting essential amino acid for mammals consuming a predominantly cereal-based diet [1,2]. The important role of Lys in promoting skeletal muscle growth has already been demonstrated in animal husbandry, and this effect was attributed to increased protein synthesis [3,4]. The functions of Lys in preventing human illnesses, such as osteoporosis and maldevelopment, have been intensively studied to protect human health [5,6]. To study the mechanism of Lys in governing skeletal muscle growth, it has been reported that the mammalian target of rapamycin complex 1 (mTORC1) pathway is activated by Lys in the skeletal muscle of rats [10]. Lys suppresses protein degradation in C2C12 myotubes via greater

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