title: Neuroendocrine regulation of autophagy by leptin.
abstract: 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.
authors.affiliation: INSERM, U848, Institut Gustave Roussy, Université Paris Sud, Villejuif, France.
authors.forename: Shoaib Ahmad
authors.initials: SA
authors.lastname: Malik
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mariño
authors.forename: Amena
authors.initials: A
authors.lastname: BenYounès
authors.forename: Shensi
authors.initials: S
authors.lastname: Shen
authors.forename: Francis
authors.initials: F
authors.lastname: Harper
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D004789:Enzyme Activation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D000077185:Resveratrol; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D020738:Leptin; C477012:MAP1LC3A protein, human; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D054411:Receptors, Leptin; D011993:Recombinant Fusion Proteins; D013267:Stilbenes; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol; D013095:Spermidine; D020123:Sirolimus