Hypothalamic AMPK-induced autophagy increases food intake by regulating NPY and POMC expression

Tae Seok Oh, Hanchae Cho, Jae Hyun Cho, Seong Woon Yu, Eun Kyoung Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Hypothalamic AMP-activated protein kinase (AMPK) plays important roles in the regulation of food intake by altering the expression of orexigenic or anorexigenic neuropeptides. However, little is known about the mechanisms of this regulation. Here, we report that hypothalamic AMPK modulates the expression of NPY (neuropeptide Y), an orexigenic neuropeptide, and POMC (pro-opiomelanocortin-α), an anorexigenic neuropeptide, by regulating autophagic activity in vitro and in vivo. In hypothalamic cell lines subjected to low glucose availability such as 2-deoxy-d-glucose (2DG)-induced glucoprivation or glucose deprivation, autophagy was induced via the activation of AMPK, which regulates ULK1 and MTOR complex 1 followed by increased Npy and decreased Pomc expression. Pharmacological or genetic inhibition of autophagy diminished the effect of AMPK on neuropeptide expression in hypothalamic cell lines. Moreover, AMPK knockdown in the arcuate nucleus of the hypothalamus decreased autophagic activity and changed Npy and Pomc expression, leading to a reduction in food intake and body weight. AMPK knockdown abolished the orexigenic effects of intraperitoneal 2DG injection by decreasing autophagy and changing Npy and Pomc expression in mice fed a high-fat diet. We suggest that the induction of autophagy is a possible mechanism of AMPK-mediated regulation of neuropeptide expression and control of feeding in response to low glucose availability.

Original languageEnglish (US)
Pages (from-to)2009-2025
Number of pages17
JournalAutophagy
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Keywords

  • appetite
  • autophagy
  • glucoprivation
  • glucose deprivation
  • hypothalamic AMPK
  • neuropeptide

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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