Abstract 19592: Exercise Training Prevents Obesity Normalizing Cardiac Mirna-208a and Med13 Levels in Obese Zucker Rats

Abstract

Aerobic 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 β-MHC content and systemic energy homeostasis via MED13, a subunit of the Mediator complex. We investigated whether ET regulates the miRNA-208a and their target MED13 related with the weight loss in obese Zucker rats (OZR). OZR (n=10) and Lean (L, n=10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT) were studied. Swimming ET consisted of 60 min of duration, 1x/day/10 weeks, with 4% caudal body weight workload. OZR groups showed a significant augment in the body weight compared with L groups. However, ET was effective in reducing weight gain in OZRT (59%) compared with OZR group. In accordance, ET reduced 20% visceral fat weight in OZRT compared with OZR group. These alterations were accompanied by resting bradycardia (12%), reduction of triglycerides (57%) and low density lipoprotein (61%) and increased of high density lipoprotein (42%) and peak VO 2 (21%) in the OZRT compared with OZR group. No difference was observed in blood pressure and glucose between groups. Cardiac miRNA-208a levels analyzed by real-time PCR increased 57% in OZR paralleled with a decrease of 39% in MED13 protein levels analyzed by western blot 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 (13%), normalized β-MHC gene and protein levels and improved the loss of diastolic function caused by obesity. These results suggest that ET can prevent weight gain via increased of cardiac MED13 and pathological cardiac hypertrophy via β-MHC reduction by regulation of miRNA-208a, indicating the heart in the systemic metabolic control and the miRNA-208a as potential therapeutic target for metabolic and cardiac disorders.