期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：6
页码：1845-1849
DOI：10.1073/pnas.1424968112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceHypothalamic agouti-related peptide (AGRP) neurons control food intake and body weight. G protein-coupled receptor 17 (GPR17) was recently shown to be expressed in these neurons and controls their activity, thereby reducing body weight and food intake in mice. In the current study, we demonstrate that Gpr17-deficient mice have normal hypothalamic and circulating AGRP levels. Body weight, food intake, and glucose homeostasis appear normal in the GPR17-deficient mice. The current data do not validate GPR17 as a therapeutic target for obesity or type 2 diabetes. G protein-coupled receptor 17 (GPR17) was recently reported to be a Foxo1 target in agouti-related peptide (AGRP) neurons. Intracerebroventricular injection of GPR17 agonists induced food intake, whereas administration of an antagonist to the receptor reduced feeding. These data lead to the conclusion that pharmacological modulation of GPR17 has therapeutic potential to treat obesity. Here we report that mice deficient in Gpr17 (Gpr17-/-) have similar food intake and body weight compared with their wild-type littermates. Gpr17-/- mice have normal hypothalamic Agrp mRNA expression, AGRP plasma levels, and metabolic rate. GPR17 deficiency in mice did not affect glucose homeostasis or prevent fat-induced insulin resistance. These data do not support a role for GPR17 in the control of food intake, body weight, or glycemic control.
