Mastaitis Jason, Min Soo, Elvert Ralf, Kannt Aimo, Xin Yurong, Ochoa Francisca, Gale Nicholas W, Valenzuela David M, Murphy Andrew J, Yancopoulos George D, Gromada Jesper
Regeneron Pharmaceuticals, Tarrytown, NY 10591; and
Regeneron Pharmaceuticals, Tarrytown, NY 10591; and.
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1845-9. doi: 10.1073/pnas.1424968112. Epub 2015 Jan 26.
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.
G蛋白偶联受体17（GPR17）最近被报道为刺鼠相关肽（AGRP）神经元中的叉头框蛋白O1（Foxo1）靶点。脑室内注射GPR17激动剂可诱导食物摄入，而给予该受体拮抗剂则会减少进食。这些数据得出结论，GPR17的药理学调节具有治疗肥胖症的潜力。在此我们报告，Gpr17基因缺失的小鼠（Gpr17(-/-)）与其野生型同窝小鼠相比，食物摄入量和体重相似。Gpr17(-/-)小鼠的下丘脑Agrp mRNA表达、AGRP血浆水平和代谢率均正常。小鼠中GPR17的缺失不影响葡萄糖稳态，也不能预防脂肪诱导的胰岛素抵抗。这些数据不支持GPR17在控制食物摄入、体重或血糖控制中起作用。
