Transition from physical activity to inactivity increases skeletal muscle miR-148b content and triggers insulin resistance.

Caroline Gastebois,Audrey Jalabert,Vincent Pialoux,Christine Durand,Sophie Rome,Stéphanie Chanon,Stéphane Blanc,Etienne Lefai,Elise Pelascini,Vanessa Euthine,Chantal Simon

doi:10.14814/phy2.12902

Abstract

This study investigated miR‐148b as a potential physiological actor of physical inactivity‐induced effects in skeletal muscle. By using animal and human protocols, we demonstrated that the early phase of transition toward inactivity was associated with an increase in muscle miR‐148b content, which triggered the downregulation of NRAS and ROCK1 target genes. Using human myotubes, we demonstrated that overexpression of miR‐148b decreased NRAS and ROCK1 protein levels, and PKB phosphorylation and glucose uptake in response to insulin. Increase in muscle miR‐148b content might thus participate in the decrease in insulin sensitivity at the whole body level during the transition toward physical inactivity.

Highlights

Current lifestyle changes, such as the increase in sedentary behaviors, are associated with higher prevalence of chronic metabolic diseases, whereas regular physical activity improves metabolic functions
Examining the consequence of a reduction in physical activity at the whole body level metabolism, it was shown that physical inactivity, which is characterized by fewer skeletal muscle contractions, is associated with decreased fat oxidation capacity (Laye et al 2009; Bergouignan et al 2013), and impaired insulin sensitivity and glycemic control (Reynolds et al 2015) in skeletal muscle
To explore miRNAs changes during the early phase of transition from an active status toward a less active behavior, we performed two complementary protocols: the LIPOX protocol in healthy lean human subjects submitted to transition from active to inactive status, and opposite (Fig. 1A); the SEDENT protocol in rodent with the wheellock model using adult mice (Fig. 1B)

Summary

Introduction

Current lifestyle changes, such as the increase in sedentary behaviors, are associated with higher prevalence of chronic metabolic diseases, whereas regular physical activity improves metabolic functions. Examining the consequence of a reduction in physical activity at the whole body level metabolism, it was shown that physical inactivity, which is characterized by fewer skeletal muscle contractions, is associated with decreased fat oxidation capacity (Laye et al 2009; Bergouignan et al 2013), and impaired insulin sensitivity and glycemic control (Reynolds et al 2015) in skeletal muscle. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society

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