Anti-apoptotic and Pro-survival Effects of Food Restriction on High-Fat Diet-Induced Obese Hearts.

Abstract

Food restriction and weight loss are known to prevent obesity-related heart diseases. This study investigates whether food restriction elicits anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats which were fed with regular chow diet (CON, 13.5% fat), a high-fat ad libitum diet (HFa, 45% fat), or a high-fat food-restricted diet (HFr, 45% fat, maintaining the same weight as CON) for 12weeks. Body weight, blood pressure, heart weight, triglycerides, insulin, HOMAIR, interstitial spaces, cardiac fibrosis, and cardiac TUNEL-positive apoptotic cells were increased in HFa relative to CON, whereas these parameters were decreased in HFr relative to HFa. The protein levels of cardiac Fas ligand, Fas receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid/Bid, Bax/Bcl-2, Bad/p-Bad, Cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) in HFr were lower than those in HFa. Moreover, the Bcl-xL and IGF-1-related components of IGF-1, p-PI3K/PI3K, p-Akt/Akt in HFr were higher than those in HFa. Our findings suggest that a restricted high-fat diet for maintaining weight control could diminish cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways as well as might enhance IGF-1-related pro-survival pathways. In sum, food restriction for maintaining normal weight could elicit anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts.