Amelioration of High Fructose-Induced Cardiac Hypertrophy by Naringin

Abstract

Heart failure is a frequent unfavorable outcome of pathological cardiac hypertrophy. Recent increase in dietary fructose consumption mirrors the rise in prevalence of cardiovascular diseases such as cardiac hypertrophy leading to concerns raised by public health experts. Mitochondria, comprising 30% of cardiomyocyte volume, play a central role in modulating redox-dependent cellular processes such as metabolism and apoptosis. Furthermore, mitochondria! dysfunction is a key cause of pathogenesis of fructose-induced cardiac hypertrophy. Naringin, a major flavanone glycoside in citrus species, has displayed strong antioxidant potential in models of oxidative stress. In this study, we evaluated protective effects of naringin against fructose-induced cardiac hypertrophy and associated mechanisms of action, using in vitro and in vivo models. We found that naringin suppressed mitochondria! ROS production and mitochondria! dysfunction in cardiomyocytes exposed to fructose and consequently reduced cardiomyocyte hypertrophy by regulating AMPK-mTOR signaling axis. Furthermore, naringin counteracted fructose-induced cardiomyocyte apoptosis, and this function of naringin was linked to its ability to inhibit ROS-dependent ATM-mediated p53 signaling. This result was supported by observations in in vivo mouse model of cardiac hypertrophy. These findings indicate a novel role for naringin in protecting against fructose-induced cardiac hypertrophy and suggest unique therapeutic strategies for prevention of cardiovascular diseases.