title: Loss of autophagy in hypothalamic POMC neurons impairs lipolysis.
abstract: Autophagy degrades cytoplasmic contents to achieve cellular homeostasis. We show that selective loss of autophagy in hypothalamic proopiomelanocortin (POMC) neurons decreases α-melanocyte-stimulating hormone (MSH) levels, promoting adiposity, impairing lipolysis and altering glucose homeostasis. Ageing reduces hypothalamic autophagy and α-MSH levels, and aged-mice phenocopy, the adiposity and lipolytic defect observed in POMC neuron autophagy-null mice. Intraperitoneal isoproterenol restores lipolysis in both models, demonstrating normal adipocyte catecholamine responsiveness. We propose that an unconventional, autophagosome-mediated form of secretion in POMC neurons controls energy balance by regulating α-MSH production. Modulating hypothalamic autophagy might have implications for preventing obesity and metabolic syndrome of ageing.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Susmita
authors.initials: S
authors.lastname: Kaushik
authors.forename: Esperanza
authors.initials: E
authors.lastname: Arias
authors.forename: Hyokjoon
authors.initials: H
authors.lastname: Kwon
authors.forename: Nuria Martinez
authors.initials: NM
authors.lastname: Lopez
authors.forename: Diana
authors.initials: D
authors.lastname: Athonvarangkul
authors.forename: Srabani
authors.initials: S
authors.lastname: Sahu
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schwartz
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Pessin
authors.forename: Rajat
authors.initials: R
authors.lastname: Singh
mesh_terms: D050154:Adiposity / Q000235:genetics; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000071193:Autophagy-Related Protein 7; D007031:Hypothalamus / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D008066:Lipolysis / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism
chemical_list: C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000071193:Autophagy-Related Protein 7