Therapeutic Effect Of Exercise Training On Cardiac Fibrotic Pathway In Obesity

Abstract

Background. No information regarding transforming growth factor beta (TGFb) and connective tissue growth factor (CTGF) in obese heart as well as no information regarding the effects of exercise training on cardiac fibrosis in obesity was available. The purpose of this study was to evaluate TGF-beta-CTGF-related fibrotic pathway in obese heart and the effects of exercise training on cardiac fibrosis. METHODS: Twelve lean Zucker rats (LZR) and twelve obese Zucker rats (OZR) at 5-6 months of age were served as sedentary lean group and sedentary obese group as well as twelve obese rats underwent swimming exercise 3 hour daily for 1 month (OZR-EX). After exercise training or sedentary status, the excised hearts were measured by Hematoxylin and Eosin (H&E) staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Masson trichrome staining and Western Blotting. RESULTS: Myocardial architecture abnormality, more cardiac TUNEL-positive apoptotic cells, and minor cardiac fibrosis were found in OZR, compared to LZR. The protein levels of TGF-beta, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), CTGF, matrix metalloproteinase (MMP)-9, and MMP2 were significantly increased in OZR relative to LZR. Exercise training decreased OZR-induced myocardial architecture abnormality, cardiac TUNEL-positive apoptotic cells, and cardiac fibrosis as well as exercise training decreased OZR-induced fibrosis-related protein levels of TGF-beta, MEK, ERK, CTGF, MMP-9, and MMP2. CONCLUSIONS: Exercise training prevented cardiac fibrosis and cardiac TGF-beta-CTGF fibrotic pathway in obese models. Our findings imply that exercise therapy could be one of possible therapeutic approaches to prevent delirious cardiac fibrosis in obesity.