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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 ?-melanocyte-stimulating hormone (MSH) levels, promoting adiposity, impairing lipolysis and altering glucose homeostasis. Ageing reduces hypothalamic autophagy and ?-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 ?-MSH production. Modulating hypothalamic autophagy might have implications for preventing obesity and metabolic syndrome of ageing.

SUBMITTER: Kaushik S

PROVIDER: S-EPMC3323137 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Loss of autophagy in hypothalamic POMC neurons impairs lipolysis.

Kaushik Susmita S Arias Esperanza E Kwon Hyokjoon H Lopez Nuria Martinez NM Athonvarangkul Diana D Sahu Srabani S Schwartz Gary J GJ Pessin Jeffrey E JE Singh Rajat R

EMBO reports 20120301 3

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 lip ...[more]

PMID: 22249165

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