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Front Endocrinol (Lausanne). 2016 Jun 27;7:76. doi: 10.3389/fendo.2016.00076. eCollection 2016.

MyomiRs as Markers of Insulin Resistance and Decreased Myogenesis in Skeletal Muscle of Diet-Induced Obese Mice.

Frontiers in endocrinology

Flávia de Toledo Frias, Mariana de Mendonça, Amanda Roque Martins, Ana Flávia Gindro, Bruno Cogliati, Rui Curi, Alice Cristina Rodrigues

Affiliations

  1. Laboratory of Pharmacogenomics, Department of Pharmacology, University of Sao Paulo , Sao Paulo , Brazil.
  2. Laboratory of Cellular Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil.
  3. Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo , Sao Paulo , Brazil.

PMID: 27445979 PMCID: PMC4921801 DOI: 10.3389/fendo.2016.00076

Abstract

High-fat diet (HFD) feeding causes insulin resistance (IR) in skeletal muscle of mice, which affects skeletal muscle metabolism and function. The involvement of muscle-specific microRNAs in the evolution of skeletal muscle IR during 4, 8, and 12 weeks in HFD-induced obese mice was investigated. After 4 weeks in HFD, mice were obese, hyperglycemic, and hyperinsulinemic; however, their muscles were responsive to insulin stimuli. Expressions of MyomiRs (miR-1, miR-133a, and miR-206) measured in soleus muscles were not different from those found in control mice. After 8 weeks of HFD feeding, glucose uptake was lower in skeletal muscle from obese mice compared to control mice, and we observed a significant decrease in miR-1a in soleus muscle when compared to HFD for 4 weeks. miR-1a expression continued to decay within time. After 12 weeks of HFD, miR-133a expression was upregulated when compared to the control group. Expression of miR-1a was negatively correlated with glycemia and positively correlated with the constant rate of plasma glucose disappearance. Pioglitazone treatment could not reverse decreases of miR-1a levels induced by HFD. Targets of myomiRs involved in insulin-growth factor (IGF)-1 pathway, such as Igf-1, Irs-1, Rheb, and follistatin, were reduced after 12 weeks in HFD and Mtor increased, when compared to the control or HFD for 4 or 8 weeks. These findings suggest for the first time that miR-1 may be a marker of the development of IR in skeletal muscle. Evidence was also presented that impairment in myomiRs expression contributes to decreased myogenesis and skeletal muscle growth reported in diabetes.

Keywords: IGF-1; high-fat diet; insulin resistance; microRNA; myogenesis; myomiRs; skeletal muscle

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