Exercise training prevents obesity-associated disorders: Role of miRNA-208a and MED13

Autor(es)

Fernandes, Tiago ^{[1, 2]} ; Barretti, Diego Lopes ^[2] ; Phillips, M. Ian ^[3] ; Oliveira, Edilamar Menezes ^[2]

Afiliação do(s) autor(es)

^[1] Harvard Med Sch, Boston Childrens Hosp, Dept Cardiol, Boston, MA - USA

^[2] Univ Sao Paulo, Sch Phys Educ & Sport, Lab Biochem & Mol Biol Exercise, Sao Paulo, SP - Brazil

^[3] Keck Grad Inst, Lab Stem Cells, Claremont, CA - USA

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 476, p. 148-154, NOV 15 2018.
• Citações Web of Science: 1

Resumo

Exercise training (ET) has been established as an important treatment for obesity, since it counteracts aberrant cardiac metabolism and weight gain; however, underlying mechanisms remain to be further determined. MicroRNAs (miRNAs) inhibit protein expression by base-pairing with the 3' UTRs of mRNA targets. MiRNA-208a is a cardiac-specific miRNA that regulates beta-MHC content and systemic energy homeostasis via MED13. We investigated whether ET regulates the cardiac miRNA-208a and its target MED13, reducing the weight gain and beta-MHC expression in obese Zucker rats (OZR). OZR (n = 11) and Lean (L, n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming ET consisted of 60 min of duration, lx/day, 5x/week/10 weeks. MiRNA and gene expression were analyzed by real-time PCR and protein levels by western blot. Resting bradycardia was observed in trained groups. ET reduced weight gain, retroperitoneal fat weight and adipocyte cell size in OZRT compared with OZR group. Cardiac miRNA-208a levels increased 57% in OZR paralleled with a decrease of 39% in MED13 protein levels compared with L group. In contrast, ET corrected the cardiac miRNA-208a and MED13 levels in OZRT compared with L group. Furthermore, ET reduced the increased cardiac mass and normalized beta-MHC protein levels caused by obesity. These results suggest that ET can prevent weight gain and pathological cardiac hypertrophy via increased of cardiac MED13 by the regulation of miRNA-208a. Therefore, miRNA-208a can be used as potential therapeutic target for metabolic and cardiac disorders. (AU)

• Processo FAPESP: 09/18370-3 - Expressão de microRNAs no coração de ratos normotensos submetidos a diferentes volumes de treinamento físico aeróbico e seu potencial terapêutico na hipertensão
• Beneficiário: Edilamar Menezes de Oliveira
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/50673-4 - A new therapeutic approach to arterial repair and regeneration by exercise training and microRNAs targeted to vasorin
• Beneficiário: Edilamar Menezes de Oliveira
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/17275-8 - Papel do microRNA-205 no déficit angiogênico mediado pela sinalização de FAK na hipertensão arterial: efeito do treinamento físico e perspectiva do potencial terapêutico
• Beneficiário: Tiago Fernandes
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/50048-1 - Bases celulares e funcionais do exercício físico na doença cardiovascular
• Beneficiário: Carlos Eduardo Negrão
• Linha de fomento: Auxílio à Pesquisa - Temático