title: MyomiRs as Markers of Insulin Resistance and Decreased Myogenesis in Skeletal Muscle of Diet-Induced Obese Mice.
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.
authors.affiliation: Laboratory of Pharmacogenomics, Department of Pharmacology, University of Sao Paulo , Sao Paulo , Brazil.
authors.forename: Flávia de Toledo
authors.initials: Fde T
authors.lastname: Frias
authors.affiliation: Laboratory of Pharmacogenomics, Department of Pharmacology, University of Sao Paulo , Sao Paulo , Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: de Mendonça
authors.affiliation: Laboratory of Cellular Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil.
authors.forename: Amanda Roque
authors.initials: AR
authors.lastname: Martins
authors.affiliation: Laboratory of Cellular Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil.
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Gindro
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of Sao Paulo , Sao Paulo , Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cogliati
authors.affiliation: Laboratory of Cellular Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo , Sao Paulo , Brazil.
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.affiliation: Laboratory of Pharmacogenomics, Department of Pharmacology, University of Sao Paulo , Sao Paulo , Brazil.
authors.forename: Alice Cristina
authors.initials: AC
authors.lastname: Rodrigues
keywords: IGF-1; high-fat diet; insulin resistance; microRNA; myogenesis; myomiRs; skeletal muscle