The satiety hormone leptin plays a cardinal role in the pathophysiology of obesity and diabetes. Here, we show that pharmacological autophagy inducers like rapamycin, spermidine and resveratrol can reduce leptin concentrations in the serum of mice and that genetic inactivation of the leptin/leptin receptor system leads to an increase in autophagy in peripheral tissues including skeletal muscle, heart and liver. Paradoxically, intravenous or intraperitoneal administration of recombinant leptin protein also induced autophagy in these tissues. Moreover, leptin stimulated canonical autophagy in cultured human or mouse cell lines, a phenomenon that was coupled to the activation of adenosine monophosphate-dependent kianse (AMPK), as well as the inhibition of mammalian target of rapamycin (mTOR), and that was confirmed by autophagic flux measurements. These results suggest that leptin plays an important role in the neuroendocrine control of autophagy, underscoring the existence of novel links between metabolic control and autophagic flux that warrant further in-depth investigation.
展开▼
