A novel adipocytokine visfatin protects against H2O2-induced myocardial apoptosis: A missing link between obesity and cardiovascular disease

Fat accumulation in obese individuals worsens the clinical outcomes of cardiovascular disease (CVD). Paradoxically, increased circulating adipocytokines secreted from visceral fat may confer cardioprotective effects. Visfatin, a novel adipocytokine, has anti-diabetic, anti-tumor, and pro-inflammatory properties. However, its effects on cardiomyocytes and the underlying mechanisms remain unknown. This article demonstrated that visfatin counteracted H2O2-induced apoptotic damage in H9c2 cardiomyocytes in a time-dependent manner. Qualitative immunofluorescence approaches demonstrated that visfatin pretreatment attenuated H2O2-induced DNA fragmentation (TdT-mediated dUTP-biotin nick end-labeling), phosphatidyl serine exposure (Annexin V/PI staining), and mitochondrial membrane potential (??m) depolarization (JC-1 staining). Biochemical studies on cardiomyoctes showed improved cell viability and reduced caspase-3 activation caused by visfatin pretreatment. Visfatin did not inhibit the death receptor-dependent apoptotic pathways, as characterized by its absence in both Fas and TNFR1 down-regulation. Instead, visfatin specifically suppressed the mitochondria-dependent apoptotic pathways, as characterized by changed levels of p53 and its downstream Bcl-2 family genes. Visfatin also up-regulated the protein levels of phosphorylated AMPK, and the anti-apoptotic action of visfatin was attenuated by the AMPK-specific inhibitor compound C. These results suggested that visfatin plays a critical role in cardioprotection by suppressing myocardial apoptosis via AMPK activation. These findings may be the missing link between obesity and CVD. J. Cell. Physiol. 228: 495501, 2013. (C) 2012 Wiley Periodicals, Inc.