Department of PharmacologyFaculty of Medicine, Dalhousie University, 5850 College Street, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2.
Department of PharmacologyFaculty of Medicine, Dalhousie University, 5850 College Street, PO Box 15000, Halifax, Nova Scotia, Canada B3H 4R2
J Endocrinol. 2014 Aug;222(2):201-15. doi: 10.1530/JOE-14-0069. Epub 2014 Jun 3.
Chemerin is an adipose-derived signaling protein (adipokine) that regulates adipocyte differentiation and function, immune function, metabolism, and glucose homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is essentially unknown. Herein, we report that expression of murine Gpr1 mRNA is high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle. In contrast to chemerin (Rarres2) and Cmklr1, Gpr1 expression predominates in the non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygous Gpr1-knockout mice fed on a high-fat diet developed more severe glucose intolerance than WT mice despite having no difference in body weight, adiposity, or energy expenditure. Moreover, mice lacking Gpr1 exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test. This study is the first, to our knowledge, to report the effects of Gpr1 deficiency on adiposity, energy balance, and glucose homeostasis in vivo. Moreover, these novel results demonstrate that GPR1 is an active chemerin receptor that contributes to the regulation of glucose homeostasis during obesity.
趋化素是一种脂肪组织来源的信号蛋白（脂肪因子），通过激活趋化因子样受体 1（CMKLR1），调节脂肪细胞分化和功能、免疫功能、代谢和葡萄糖稳态。在哺乳动物中，趋化素的第二个受体，G 蛋白偶联受体 1（GPR1），与 CMKLR1 具有相似的亲和力结合趋化素；然而，GPR1 在哺乳动物中的功能基本上是未知的。在此，我们报告鼠 Gpr1 mRNA 的表达在棕色脂肪组织和白色脂肪组织（WAT）和骨骼肌中很高。与趋化素（Rarres2）和 Cmklr1 相反，Gpr1 的表达在 WAT 的非脂肪细胞基质血管部分占优势。尽管体重、肥胖或能量消耗没有差异，杂合子和纯合子 Gpr1 敲除小鼠在高脂肪饮食下比 WT 小鼠更容易出现严重的葡萄糖不耐受。此外，缺乏 Gpr1 的小鼠在丙酮酸耐量试验中表现出较低的葡萄糖刺激胰岛素水平和升高的葡萄糖水平。本研究首次报道了 Gpr1 缺乏对体内肥胖、能量平衡和葡萄糖稳态的影响。此外，这些新的结果表明 GPR1 是一种活跃的趋化素受体，有助于肥胖期间葡萄糖稳态的调节。
