Gpr17 in AgRP neurons regulates feeding and sensitivity to insulin and leptin

Hongxia Ren, Joshua R. Cook, Ning Kon, Domenico Accili

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Hypothalamic neurons expressing agouti-related peptide (AgRP) regulate eating and glucose metabolism. Ablation of FOXO1 in AgRP neurons of mice results in reduced food intake, leanness, improved glucose homeostasis, and increased sensitivity to insulin and leptin. We tentatively identified G-protein-coupled receptor Gpr17 as an effector of FOXO1 orexigenic signals in AgRP neurons. In this study, we generated and characterized AgRP neuron-specific Gpr17 knockout mice (Agrp-Gpr17-/-) to test the hypothesis that Gpr17 regulates appetite, energy expenditure, and metabolism. Agrp-Gpr17-/- mice show reduced food intake, increased relative energy expenditure, and increased satiety, resulting in leanness and reduced body fat. They also show increased central nervous system sensitivity to insulin and leptin and reduced plasma glucose excursions following the administration of glucose or pyruvate. In summary, AgRP neuron-specific Gpr17 knockouts phenocopy FOXO1 knockouts in the same cell type, thus supporting our original hypothesis and providing further impetus to develop Gpr17 antagonists for the treatment of obesity.

Original languageEnglish (US)
Pages (from-to)3670-3679
Number of pages10
JournalDiabetes
Volume64
Issue number11
DOIs
StatePublished - Nov 2015
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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