Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin

Qian Wang, Chen Liu, Aki Uchida, Jen Chieh Chuang, Angela Walker, Tiemin Liu, Sherri Osborne-Lawrence, Brittany L. Mason, Christina Mosher, Eric D. Berglund, Joel K. Elmquist, Jeffrey M. Zigman

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreERT2 transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia.

Original languageEnglish (US)
Pages (from-to)64-72
Number of pages9
JournalMolecular Metabolism
Volume3
Issue number1
DOIs
StatePublished - Feb 1 2014

Keywords

  • AgRP
  • Blood glucose homeostasis
  • Food intake
  • Ghrelin
  • Ghrelin receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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