Acute Succinate Administration Increases Oxidative Phosphorylation and Skeletal Muscle Explosive Strength via SUCNR1.

Guli Xu,Yexian Yuan,Pei Luo,Jinping Yang,Canjun Zhu,Gang Shu,Qingyan Jiang,Jingjing Zhou

doi:10.3389/fvets.2021.808863

Guli Xu, Yexian Yuan + Show 6 more

Open Access

https://doi.org/10.3389/fvets.2021.808863

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Abstract

Endurance training and explosive strength training, with different contraction protein and energy metabolism adaptation in skeletal muscle, are both beneficial for physical function and quality of life. Our previous study found that chronic succinate feeding enhanced the endurance exercise of mice by inducing skeletal muscle fiber-type transformation. The purpose of this study is to investigate the effect of acute succinate administration on skeletal muscle explosive strength and its potential mechanism. Succinate was injected to mature mice to explore the acute effect of succinate on skeletal muscle explosive strength. And C2C12 cells were used to verify the short-term effect of succinate on oxidative phosphorylation. Then the cells interfered with succinate receptor 1 (SUCNR1) siRNA, and the SUCNR1-GKO mouse model was used for verifying the role of SUCNR1 in succinate-induced muscle metabolism and expression and explosive strength. The results showed that acute injection of succinate remarkably improved the explosive strength in mice and also decreased the ratio of nicotinamide adenine dinucleotide (NADH) to NAD+ and increased the mitochondrial complex enzyme activity and creatine kinase (CK) activity in skeletal muscle tissue. Similarly, treatment of C2C12 cells with succinate revealed that succinate significantly enhanced oxidative phosphorylation with increased adenosine triphosphate (ATP) content, CK, and the activities of mitochondrial complex I and complex II, but with decreased lactate content, reactive oxygen species (ROS) content, and NADH/NAD+ ratio. Moreover, the succinate's effects on oxidative phosphorylation were blocked in SUCNR1-KD cells and SUCNR1-KO mice. In addition, succinate-induced explosive strength was also abolished by SUCNR1 knockout. All the results indicate that acute succinate administration increases oxidative phosphorylation and skeletal muscle explosive strength in a SUCNR1-dependent manner.

Highlights

Skeletal muscle function is a crucial prerequisite to ensure quality of life, in physical exercise, and in athletic sports
Acetyl-CoA produced from glycolysis of glucose, oxidation of pyruvate, and β-oxidation of fatty acid produces nicotinamide adenine dinucleotide (NADH) by tricarboxylic acid (TCA) cycle to generate adenosine triphosphate (ATP) [3]
SgRNAs of succinate receptor 1 (SUCNR1) were knocked into zygotes in vitro to delete exon 2 of SUCNR1 by clustering regularly, interspaced short palindromic repeats Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated proteins 9 (CRISPR-Cas9) systems, and the embryo was transferred to pseudo-pregnant recipients to obtain F0 generation

Summary

Introduction

Skeletal muscle function is a crucial prerequisite to ensure quality of life, in physical exercise, and in athletic sports. Based on muscle contraction intensity and time, endurance exercise, and resistance exercise require different contraction units and energy metabolism patterns [1]. Endurance exercises are mainly dependent on the aerobic metabolism of glucose and fatty acid [2]. Acetyl-CoA produced from glycolysis of glucose, oxidation of pyruvate, and β-oxidation of fatty acid produces nicotinamide adenine dinucleotide (NADH) by tricarboxylic acid (TCA) cycle to generate adenosine triphosphate (ATP) [3]. The latter relies on the glycolysis of glucose and glycogen to produce ATP rapidly with a byproductlactate accumulation [4]. Individuals with stronger endurance exercise usually have weaker explosive power, and vice versa

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