Loss of autophagy in hypothalamic POMC neurons impairs lipolysis

EMBO Rep. 2012 Mar 1;13(3):258-65. doi: 10.1038/embor.2011.260.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics
  • Aging / genetics
  • Aging / metabolism
  • Animals
  • Autophagy / genetics*
  • Autophagy-Related Protein 7
  • Hypothalamus / metabolism*
  • Insulin Resistance / genetics
  • Lipolysis / genetics*
  • Male
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Neurons / metabolism*
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism*
  • alpha-MSH / metabolism


  • Atg7 protein, mouse
  • Microtubule-Associated Proteins
  • alpha-MSH
  • Pro-Opiomelanocortin
  • Autophagy-Related Protein 7