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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 476, p. 148-154, NOV 15 2018.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 14/50673-4 - A new therapeutic approach to arterial repair and regeneration by exercise training and microRNAs targeted to vasorin
• Grantee: Edilamar Menezes de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/17275-8 - Role of microRNA-205 in the angiogenic deficit mediated by FAK signaling in hypertension: effect of exercise training and perspective of the therapeutic potential
• Grantee: Tiago Fernandes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/18370-3 - microRNA expression on normotensive rats heart submitted to different aerobic training and the potential to hypertension therapy.
• Grantee: Edilamar Menezes de Oliveira
• Support Opportunities: Regular Research Grants