The Coexistence of Aging and Obesity Additively Increase Cardiac Apoptosis

Abstract

PURPOSE: Cardiac apoptosis were found in obesity, but the cardiac molecular mechanism in the aging obesity were not available. The purpose of this study was to evaluate whether the aging and obesity will additively influence the apoptotic pathways. METHODS: Eleven young lean (YL), 10 young obese (YO), 11 old lean (OL), and 11 old obese (OO) Zucker rats were investigated at 4 and 14 months old. The cardiac characteristics, apoptotic levels and their related pathways in the excised left ventricle form rats were measured by heart weight index, histological analysis, positive TUNEL assays, H&E stain, and Western blotting. RESULTS: Compared with YL group, the whole heart weight, the abnormal myocardial architecture, and TUNEL-positive apoptotic cells were significantly higher in YO, OL or OO groups. The activity of cardiac Fas receptor-dependent apoptotic pathway (Fas L, Fas, FADD, caspase-8, caspase-3), mitochondrial -dependent apoptotic pathway (Bad, cytosolic cytochrome c, caspase-9,, caspase-3) and transition from Fas- to mitochondrial-dependent apoptotic pathway (tBid) were significantly higher in YO, OL or OO groups than those in YL group. These pathways were higher in OO group than either YO or OL groups. CONCLUSIONS: The coexistence of aging and obesity additively increase cardiac Fas receptor and mitochondrial -dependent apoptosis. These findings may provide a possible apoptotic mechanism for developing heart failure in aging obesity.