Transition from physical activity to inactivity increases skeletal muscle miR-148b content and triggers insulin resistance.
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.
CarMeN Laboratory, INSERM U1060 INRA 1397 University of Lyon 1, Oullins, France.
Caroline
C
Gastebois
CarMeN Laboratory, INSERM U1060 INRA 1397 University of Lyon 1, Oullins, France.
Stéphanie
S
Chanon
CarMeN Laboratory, INSERM U1060 INRA 1397 University of Lyon 1, Oullins, France.
Sophie
S
Rome
CarMeN Laboratory, INSERM U1060 INRA 1397 University of Lyon 1, Oullins, France.
Christine
C
Durand
Department of Digestive and Bariatric Surgery, Hospices Civils de Lyon, Lyon, France.
Elise
E
Pelascini
CarMeN Laboratory, INSERM U1060 INRA 1397 University of Lyon 1, Oullins, France.
Audrey
A
Jalabert
CarMeN Laboratory, INSERM U1060 INRA 1397 University of Lyon 1, Oullins, France.
Vanessa
V
Euthine
Laboratoire LIBM EA 7424, University of Lyon, Lyon, France.
Vincent
V
Pialoux
Institut Pluridisciplinaire Hubert Curien, CNRS UMR 7178 University of Strasbourg, Strasbourg, France.
Stéphane
S
Blanc
CarMeN Laboratory, INSERM U1060 INRA 1397 University of Lyon 1, Oullins, France.
Chantal
C
Simon
CarMeN Laboratory, INSERM U1060 INRA 1397 University of Lyon 1, Oullins, France etienne.lefai@univ-lyon1.fr.
Etienne
0000-0002-3042-7801
E
Lefai
D000328:Adult; D000818:Animals; D015444:Exercise / Q000502:physiology*; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D057185:Sedentary Behavior; D054460:rho-Associated Kinases / Q000378:metabolism
D007328:Insulin; C550570:MIRN148 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C554644:Mirn148 microRNA, mouse; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
Insulin‐signaling pathway; miRNA; muscle tissue; myotube; physical inactivity