MicroRNA miR-222 mediates pioglitazone beneficial effects on skeletal muscle of diet-induced obese mice

Autor(es):Mostrar menos -

de Mendonca, Mariana ^[1] ; de Sousa, Erica ^[1] ; da Paixao, Ailma O. ^[1] ; dos Santos, Bruna Araujo ^[1] ; Spagnol, Alexandre Roveratti ^[1] ; Murata, Gilson M. ^[2] ; Araujo, Hygor N. ^{[3, 4]} ; de Lima, Tanes Imamura ^{[3, 4]} ; Passos Simoes Froes Guimaraes, Dimitrius Santiago ^{[3, 4]} ; Silveira, Leonardo R. ^{[3, 4]} ; Rodrigues, Alice C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, SP - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[4] Obes & Comorbid Res Ctr, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 501, FEB 5 2020.
• Citações Web of Science: 0

Resumo

Pioglitazone belongs to the class of drugs thiazolidinediones (TZDs) and is an oral hypoglycemic drug, used in the treatment of type 2 diabetes, which improves insulin sensitivity in target tissues. Adipose tissue is the main target of pioglitazone, a PPARg and PPARa agonist; however, studies also point to skeletal muscle as a target. Non-PPAR targets of TZDs have been described, thus we aimed to study the direct effects of pioglitazone on skeletal muscle and the possible role of microRNAs as targets of this drug. Pioglitazone treatment of obese mice increased insulin-mediated glucose transport as a result of increased fatty acid oxidation and mitochondrial activity. PPARg blockage by treatment with GW9662 nullified pioglitazone's effect on systemic and muscle insulin sensitivity and citrate synthase activity of obese mice. After eight weeks of high-fat diet, miR-221-3p expression in soleus muscle was similar among the groups and miR-23b-3p and miR-222-3p were up-regulated in obese mice compared to the control group, and treatment with pioglitazone was able to reverse this condition. In vitro studies in C2C12 cells suggest that inhibition of miR-222-3p protects C2C12 cells from insulin resistance and increased non-mitochondrial respiration induced by palmitate. Together, these data demonstrate a role of pioglitazone in the downregulation of microRNAs that is not dependent on PPARg. Moreover, miR-222 may be a novel PPARg-independent mechanism through which pioglitazone improves insulin sensitivity in skeletal muscle. (AU)

• Processo FAPESP: 14/22046-5 - Efeito da pioglitazona na expressão de microRNAs do músculo esquelético de camundongos com obesidade induzida por dieta hiperlipídica
• Beneficiário: Mariana de Mendonça
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/24789-8 - MicroRNAs na via de sinalização de adiponectina: possíveis alvos terapêuticos na melhora da resistência à insulina e de doenças associadas.
• Beneficiário: Alice Cristina Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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
• Processo FAPESP: 15/24650-0 - Papel do microRNAs no controle da expressão gênica de adiponectina
• Beneficiário: Mariana de Mendonça
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica