TLR4-Mediated Inflammatory Responses Regulate Exercise-Induced Molecular Adaptations in Mouse Skeletal Muscle.

Haruna Fujiyoshi,Tatsuya Hayashi,Takumi Yokokawa,Tatsuro Egawa,Eriko Kurogi,Kohei Kido

doi:10.3390/ijms23031877

Abstract

Endurance exercise induces various adaptations that yield health benefits; however, the underlying molecular mechanism has not been fully elucidated. Given that it has recently been accepted that inflammatory responses are required for a specific muscle adaptation after exercise, this study investigated whether toll-like receptor (TLR) 4, a pattern recognition receptor that induces proinflammatory cytokines, is responsible for exercise-induced adaptations in mouse skeletal muscle. The TLR4 mutant (TLR4m) and intact TLR4 control mice were each divided into 2 groups (sedentary and voluntary wheel running) and were housed for six weeks. Next, we removed the plantaris muscle and evaluated the expression of cytokines and muscle regulators. Exercise increased cytokine expression in the controls, whereas a smaller increase was observed in the TLR4m mice. Mitochondrial markers and mitochondrial biogenesis inducers, including peroxisome proliferator-activated receptor beta and heat shock protein 72, were increased in the exercised controls, whereas this upregulation was attenuated in the TLR4m mice. In contrast, exercise increased the expression of molecules such as peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and glucose transporter 4 in both the controls and TLR4m mice. Our findings indicate that exercise adaptations such as mitochondrial biogenesis are mediated via TLR4, and that TLR4-mediated inflammatory responses could be involved in the mechanism of adaptation.

Highlights

Endurance exercise induces various types of adaptations and contributes to health, especially in skeletal muscles, which constitute approximately 40% of body weight
To confirm whether the skeletal muscle inflammatory response of the TLR4 mutant (TLR4m) mice was was defective, we preliminarily examined the mRNA expression of proinflammatory defective, we preliminarily examined the mRNA expression of proinflammatory cytokines tokines in response to LPS (Figure 1)
IL-6 (p < 0.001) (Figure 1C). mRNA expression was remarkably increased after LPS in (p < 0.001) (Figure 1C). mRNA expression was remarkably increased after LPS injection in tion in the controls, whereas the increased effects were attenuated in the TLR4m mic the controls, whereas the increased effects were attenuated in the TLR4m mice

Summary

Introduction

Endurance exercise induces various types of adaptations and contributes to health, especially in skeletal muscles, which constitute approximately 40% of body weight. A short period of intense exercise increases glucose uptake and energy consumption in skeletal muscle [1,2], and continuous exercise training increases insulin sensitivity [3,4] and mitochondrial biogenesis [5,6,7]. This exercise-induced mitochondrial adaptation leads to higher oxidative capacity, and the energy supply system changes from glycolytic to oxidative [5,8], thereby adapting skeletal muscles to endurance exercise.

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