title: More activated cardiac mitochondrial-dependent apoptotic pathway in obese Zucker rats.
abstract: 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.
authors: Department of Internal Medicine, Chung-Shan Medical University and Hospital, Taichung, Taiwan.
authors: Min-Chi
authors: MC
authors: Lu
authors: Bor-Show
authors: BS
authors: Tzang
authors: Wei-Wen
authors: WW
authors: Kuo
authors: Fong-Li
authors: FL
authors: Wu
authors: Yueh-Sheng
authors: YS
authors: Chen
authors: Chang-Hai
authors: CH
authors: Tsai
authors: Chih-Yang
authors: CY
authors: Huang
authors: Shin-Da
authors: SD
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000502:physiology*; D024101:Mitochondrial Proteins; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: C505650:BNIP3 protein, rat; C494821:Bad protein, rat; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D051025:bcl-Associated Death Protein; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9