Involvement of autophagy in the effect of exercise on left ventricular hypertrophy induced by high fat diet in rats

Abstract

Objectives: Left ventricular hypertrophy (LVH) associated with obesity increases the morbidity and mortality of cardiovascular disease, which could be attenuated by exercise in overweight and hypertensive patients. The lysosomal degradation pathway − autophagy is reportedly mediated the beneficial effect of exercise on glucose and lipid homeostasis. The present study aimed to investigate the involvement of autophagy in the effect of exercise on LVH induced by high fat diet in rats. Methods: Female adult SD rats were divided into 4 groups namely: (i) high fat diet (HFD), (ii) HFD+exercise, (iii) exercise, (iv) control. Rats in the HFD groups were orally fed with high-fat chow (30% fat) daily for 12 weeks, and rats in the exercise groups had exercise with a motorized wheel in the last 4 weeks. Noninvasive measures of systolic pressure and fat composition were assessed, respectively by tail cuff and MRI. The expression of markers for cardiac hypertrophy and the protein expression in autophagic pathway were determined by quantitative real time-PCR and western blot, respectively. Statistical significance was at p<0.05 with ANOVA analysis followed by post-hoc tests. Results: Rats fed with HFD had LVH (increased heart weight and LV/ RV+septum ratio) with higher levels of body weight, arterial pressures and fat composition than that of the control rat. In addition, the QTc interval and

the diameter and disarray of ventricular myocytes were significantly increased in the HFD group, supported by elevated levels of the expression of hypertrophic markers (ANP, BNP, β-MHC). These parameters were attenuated by exercise in the HFD-fed rats. Moreover, we found elevated levels of LC3II in the HFD heart, which were also attenuated by exercise, suggesting an involvement of autophagy in the beneficial effect of exercise. Furthermore, the expression level of AMPKα was also increased in the exercise groups. Conclusion: We demonstrated that exercise lowers the body weight and attenuates the HFD-induced LVH in rats, which probably involves autophagy. Future studies will focus on the role of autophagy in the pathogenesis.