Exercise May Promote Skeletal Muscle Hypertrophy via Enhancing Leucine-Sensing: Preliminary Evidence.

Yan Zhao,Zhi Xia,Yueqin Yang,Qianjin Wang,Xiaomin Ding,Shaosheng Liu,Huayu Shang,Nelo Eidy Zanchi,Jason Cholewa

doi:10.3389/fphys.2021.741038

Abstract

Several studies have indicated a positive effect of exercise (especially resistance exercise) on the mTOR signaling that control muscle protein synthesis and muscle remodeling. However, the relationship between exercise, mTOR activation and leucine-sensing requires further clarification. Two month old Sprague-Dawley rats were subjected to aerobic exercise (treadmill running at 20 m/min, 6° incline for 60 min) and resistance exercise (incremental ladder climbing) for 4 weeks. The gastrocnemius muscles were removed for determination of muscle fibers diameter, cross-sectional area (CSA), protein concentration and proteins involved in muscle leucine-sensing and protein synthesis. The results show that 4 weeks of resistance exercise increased the diameter and CSA of gastrocnemius muscle fibers, protein concentration, the phosphorylation of mTOR (Ser2448), 4E-BP1(Thr37/46), p70S6K (Thr389), and the expression of LeuRS, while aerobic exercise just led to a significant increase in protein concentration and the phosphorylation of 4E-BP1(Thr37/46). Moreover, no difference was found for Sestrin2 expression between groups. The current study shows resistance exercise, but not aerobic exercise, may increase muscle protein synthesis and protein deposition, and induces muscle hypertrophy through LeuRS/mTOR signaling pathway. However, further studies are still warranted to clarify the exact effects of vary intensities and durations of aerobic exercise training.

Highlights

Age-related Sarcopenia (ArS) is a phenomenon of skeletal muscle atrophy and functional decline with advancing age (Bauer et al, 2019)
As for the multiple comparison between groups, the cross-sectional area (CSA) (P < 0.01) and diameter (P < 0.01) of resistance exercise-trained group (RE) group were significantly greater than the gastrocnemius of sedentary control group (SC) group, and the diameter were greater than the aerobic exercise-trained group (AE) group (P < 0.05); between AE and SC groups, no statistical significance could be detected (Figure 1)
We observed a significant increase in the CSA and diameter of gastrocnemius muscle fibers, gastrocnemius wet weight, muscle protein concentration, the phosphorylation state of mTOR signaling, and the relative expression of Leucyl-tRNA synthetase (LeuRS) in resistance exercise-trained rats

Summary

Introduction

Age-related Sarcopenia (ArS) is a phenomenon of skeletal muscle atrophy and functional decline with advancing age (Bauer et al, 2019). Rag GTPase is the mediator of the mTORC1 pathway in response to nutrient stimulation, the proteogenic amino acid leucine. RagA-RagC and RagB-RagD, respectively, from heterodimers to regulate mTORC1 activation induced by different amino acids (Sancak et al, 2008; Lee et al, 2018). In response to leucine stimulation, mTORC1 translocates from the cytoplasm to the surface of lysosomes, interacting with the active heterodimer formed by GTP-loaded RagB and GDP-loaded RagD, and activates its downstream molecular events (Sancak et al, 2008, 2010). In the process of promoting skeletal muscle protein synthesis and inducing adaptive hypertrophy mediated by mTORC1 in response to anabolic stimulation, a leucine sensor must be involved as a rate-limiting factor. Which proteins are involved as leucine sensors in skeletal muscle, and how they participate in regulation is not fully understood (Lushchak et al, 2019)

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