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

Physiol Rep. 2016 Sep;4(17):e12902. 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.

Keywords: Insulin‐signaling pathway; miRNA; muscle tissue; myotube; physical inactivity.

MeSH terms

  • Adult
  • Animals
  • Exercise / physiology*
  • Female
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance / physiology*
  • Male
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology*
  • Phosphorylation
  • Sedentary Behavior
  • rho-Associated Kinases / metabolism

Substances

  • Insulin
  • MIRN148 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Mirn148 microRNA, mouse
  • ROCK1 protein, human
  • rho-Associated Kinases
  • GTP Phosphohydrolases
  • NRAS protein, human