Current pharmaceutical design
-
Leptin hormone plays a vital role in the pathophysiological changes in heart geometry and function. Nonetheless, the precise mechanism(s) triggering leptin-induced cardiomyocyte contractile dysfunction is not well understood. The present study was designed to examine if autophagy plays a role in leptin-induced cardiac contractile anomalies. ⋯ Pharmacological inhibition of reactive oxygen species (ROS) using tempol significantly attenuated leptin-induced autophagosome formation and cardiac contractile anomalies. In addition, genetic deletion of AMPKα2 or pharmacological inhibition of AMPK using compound C abrogated leptin or superoxide induced cardiac contractile dysfunction and autophagosome formation. In summary, our data revealed that leptin impairs cardiac contractile function through a superoxide generation-AMPK activation-and autophagy dependent mechanism.