Loss of autophagy in hypothalamic POMC neurons impairs lipolysis

Susmita Kaushik, Esperanza Arias, Hyokjoon Kwon, Nuria Martinez Lopez, Diana Athonvarangkul, Srabani Sahu, Gary J. Schwartz, Jeffrey E. Pessin, Rajat Singh

Research output: Contribution to journalArticle

91 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)258-265
Number of pages8
JournalEMBO Reports
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2012

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Keywords

  • POMC
  • ageing
  • autophagy
  • hypothalamus
  • obesity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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