OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin.

Li, Erwei; Shan, Haili; Chen, Liqun; Long, Aijun; Zhang, Yuanyuan; Liu, Yang; Jia, Liangjie; Wei, Fangchao et al. · Cell Metab · 2019

basic_science · Level V

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Abstract

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.

Medical subject headings