Myomirs as Markers of insulin resistance and Decreased Myogenesis in skeletal Muscle of Diet-induced Obese Mice

Autor(es)

Frias, Flavia de Toledo ; de Mendonca, Mariana ; Martins, Amanda Roque ; Gindro, Ana Flavia ; Cogliati, Bruno ; Curi, Rui ; Rodrigues, Alice Cristina

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ENDOCRINOLOGY; v. 7, JUN 27 2016.
• Citações Web of Science: 6

Resumo

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. (AU)

• Processo FAPESP: 11/05876-6 - Avaliação de microRNAs no desenvolvimento da resistência à insulina
• Beneficiário: Alice Cristina Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores