Cardiac fas receptor-dependent apoptotic pathway in obese Zucker rats.
OBJECTIVE
Very limited information regarding the cardiac molecular mechanism in obesity is available. The purpose of this study was to evaluate the cardiac Fas receptor-dependent (type I) apoptotic pathway in obese Zucker rats.


METHODS
Sixteen obese Zucker rats were studied at 5 to 6 months of age, and 16 age-matched lean Zucker rats served as controls. Heart weight index, myocardial architecture, key components of the Fas receptor-dependent apoptotic pathway, apoptotic activity, and fibrosis in the excised left ventricle of rats were measured by weight scales, hematoxylin and eosin staining, Western blotting, TUNEL assay, and Masson trichrome staining.


RESULTS
Body weight, whole heart weight, left ventricular weight, ratio of whole heart weight to tibia length, percentage of TUNEL-positive cardiac myocytes, and percentage of cardiac fibrosis were significantly increased in the obese group. Cardiomyocyte disarray and increased cardiac interstitial space were observed in obese rats. Protein levels of Fas ligand, Fas death receptors, and Fas-associated Death Domain were all significantly increased in the obese group. In addition, pro-caspase-8 and pro-caspase-3 were significantly decreased, whereas activated caspase-8 and activated caspase-3 were significantly increased in the obese group, which implies that pro-forms of caspase-8 and caspase-3 were cleaved into active-forms caspase-8 and caspase-3.


CONCLUSIONS
Cardiac Fas receptor-dependent apoptotic pathways were more activated in obese rats' hearts, which may provide one of the possible apoptotic mechanisms for developing cardiac abnormality in obesity.
Lee
Shin-Da
SD
Department of Physical Therapy, China Medical University, Taichung, Taiwan.
Tzang
Bor-Show
BS
Kuo
Wei-Wen
WW
Lin
Yueh-Min
YM
Yang
Ai-Lan
AL
Chen
Szu-Hua
SH
Tsai
Fuu-Jen
FJ
Wu
Fong-Li
FL
Lu
Min-Chi
MC
Huang
Chih-Yang
CY
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D053181:Caspase 8 / Q000032:analysis / Q000378:metabolism; D005355:Fibrosis; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011924:Rats, Zucker; D053218:Receptors, Death Domain / Q000819:agonists* / Q000378:metabolism; D019014:fas Receptor / Q000819:agonists* / Q000378:metabolism
D053218:Receptors, Death Domain; D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8