OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin
OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin
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DOI：
10.1016/j.cmet.2019.05.022
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发表时间：
2019-08-06
期刊：
影响因子：
29
通讯作者：
Wang, Yiguo
中科院分区：
文献类型：
--
作者：
Li, Erwei;Shan, Haili;Wang, Yiguo
白脂素是一种禁食诱导的激素，可通过未知的 G 蛋白偶联受体 (GPCR) 激活 cAMP 信号通路，从而促进肝脏中葡萄糖的产生并刺激下丘脑的食欲。然而，白脂素的真正受体尚不清楚。在这里，我们发现嗅觉受体 OLFR734 作为 Asprosin 的受体来调节肝葡萄糖的产生。 Olfr734 基因敲除小鼠对 Asprosin 的反应减弱，包括 cAMP 水平和肝葡萄糖生成减弱，以及胰岛素敏感性提高。由于 Olfr734 缺乏会显着减弱禁食和高脂肪饮食诱导的葡萄糖产生，因此我们的结果证明 OLFR734 作为 Asprosin 受体在维持禁食和肥胖期间的葡萄糖稳态方面发挥着关键作用。
Asprosin is a fasting-induced hormone that promotes glucose production in the liver and stimulates appetite in the hypothalamus by activating the cAMP signaling pathway via an unknown G protein-coupled receptor (GPCR). However, the bona fide receptor of Asprosin is unclear. Here, we have identified that the olfactory receptor OLFR734 acts as a receptor of Asprosin to modulate hepatic glucose production. Olfr734 knockout mice show a blunted response to Asprosin, including attenuated cAMP levels and hepatic glucose production, and improved insulin sensitivity. As Olfr734 deficiency dramatically attenuates both fasting and high-fat-diet-induced glucose production, our results demonstrate a critical role of OLFR734 as a receptor of Asprosin to maintain glucose homeostasis during fasting and in obesity.