Obesity is associated with an increasing prevalence of
cardiovascular diseases and
metabolic syndrome. It is of paramount importance to reduce
obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the
AMP-activated protein kinase (AMPK) pathway by
punicalagin (PU), a major
ellagitannin in pomegranate was investigated in the heart of a rat
obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40%
punicalagin sufficiently prevented high-fat diet (HFD)-induced
obesity associated accumulation of cardiac
triglyceride and
cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II
enzymes in the hearts of HFD rats. Together with the normalized expression of
uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac
ATP loss. Through in vitro cultures, we showed that
punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular
ATP/
ADP ratio specifically in cardiomyocytes. Our findings demonstrated that
punicalagin, the major active component in PE, could modulate mitochondria and phase II
enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders.