Possible pathophysiology of heart failure in obesity: Cardiac apoptosis

Obesity has traditionally been considered an independent risk factor for heart failure whose pathophysiology is generally believed to associated with the consequence of myocyte hypertrophy, myocardial fibrosis, and abnormalities of intracellular calcium handling. Obesity-related comorbities like chronic inflammation, coronary artery disease, diabetes, and hypertension play some causative roles in the development of heart failure. Currently, cardiac apoptosis and cardiac fibrosis are found in obesity and leptin-deficient animal models. Leptin pretreatment exerts antiapoptotic effects in cardiomyocytes. In obese rat hearts, key components of Fas-dependent apoptosis (Fas ligand, tumor necrosis factor-alpha, Fas death receptors, Fas-associated death domain, activated caspase 8, and activated caspase 3) as well as those of mitochondria-dependent apoptosis (Bad, Bax, Bax-to-Bcl2 ratio, cytosolic cytochrome c, activated caspase 9, and activated caspase 3) manifestly increased compared with lean controls. Obesity will activate cardiac Fas- and mitochondria-dependent apoptotic pathways while increasing cardiac fibrosis, which may provide one of the possible mechanisms for developing heart failure in obesity.