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Publication
Gpr17 in AgRP Neurons Regulates Feeding and Sensitivity to Insulin and Leptin.
Authors Ren H, Cook JR, Kon N, Accili D
Submitted By Submitted Externally on 7/27/2017
Status Published
Journal Diabetes
Year 2015
Date Published
Volume : Pages 64 : 3670 - 9
PubMed Reference 26180086
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.






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