Accumulating studies have demonstrated that the autophagy–lysosome pathway, a major pathway governing protein and organelle degradation and recycling, is a house keeper in cardiomyocytes under physiological conditions (Mizushima and Klionsky, 2007). However, the role of autophagy in the heart under pathological conditions is still controversial (Nemchenko et al., 2011). In vivo studies depicted that inhibition of mammalian target of rapamycin (mTOR), a primary inhibitory regulator of autophagy, is capable of attenuating pressure overload-induced cardiac dysfunction (McMullen et al., 2004). To the contrary, recent studies have also indicated that suppressing autophagy is beneficial for cardiac hypertrophy (Cao et al., 2011). Along the same line, activated autophagy has been proved detrimental for pressure overload-induced heart failure (Zhu et al., 2007). However, the role of autophagy in the heart in high-fat diet (HFD)-induced obesity is poorly understood.
To date, there is little evidence suggesting a role of autophagy in heart anomalies associated with diet-induced obesity, although a number of upstream regulators of autophagy have been identified to play a role in HFD-induced obesity. For example, the primary inhibitor of autophagy mTOR may be hyperactivated by an HFD and contribute to the development of cardiac dysfunction (Birse et al., 2010). As the major activator of mTOR, the Akt family of serine–threonine kinases is also activated by an HFD in the heart. However, the precise role of Akt2, one of the three Akt isoforms predominantly found in the heart, in autophagy regulation in HFD-induced obesity still remains elusive. To this end, the present study was designed to evaluate the role of autophagy and autophagy flux in HFD feeding-induced cardiac geometric and functional changes with a special focus on Akt2 signaling.