Background: Obesity is often associated with the development of heart failure, but the precise mechanisms remain uncertain. The purpose of this study was to evaluate the key components of the mitochondrial-dependent apoptotic pathway in excised heart from obese Zucker rats.
Methods: Twelve obese Zucker rats were studied at 5 to 6 months of age, and 12 age-matched lean Zucker rats served as control. The myocardial architecture and key components of the mitochondrial-dependent apoptotic pathway in the excised left ventricle from rats were measured by histopathological analysis, Western blotting, and reverse transcription polymerase chain reaction (RT-PCR).
Results: The ratios of whole heart weight to tibia length were significantly increased in the obese group. Cardiomyocyte disarray, the increased interstitial space, and minor cardiac fibrosis were observed in obese rat hearts. Pro-apoptotic Bcl2 family members, Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3) and Bad levels, were significantly increased in obese rat hearts, whereas anti-apoptotic Bcl2 family member, Bcl2 level, was significantly decreased. Cytosolic cytochrome c indicating cytochrome c release from mitochondria was significantly increased in obese rat heart. In addition, upstream pro-caspase-9 and pro-caspase-3 were significantly decreased, whereas activated caspase-9 and activated caspase-3 were significantly increased in obese rat hearts, compared with lean rat heart, implying that pro-forms of caspase-9 and caspase-3 were cleaved into active-forms caspase-9 and caspase-3.
Conclusions: The cardiac mitochondrial-dependent apoptotic pathway was more activated in obese Zucker rats than in lean rats, which may provide one possible apoptotic mechanism for developing heart failure in obesity.