OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin

  • Cell Metab. 2019 Aug 6;30(2):319-328.e8. doi: 10.1016/j.cmet.2019.05.022.
Erwei Li  1 ,  Haili Shan  1 ,  Liqun Chen  1 ,  Aijun Long  1 ,  Yuanyuan Zhang  1 ,  Yang Liu  1 ,  Liangjie Jia  1 ,  Fangchao Wei  1 ,  Jinbo Han  1 ,  Tong Li  1 ,  Xiaohui Liu  2 ,  Haiteng Deng  3 ,  Yiguo Wang  4
Affiliations
  • 1. MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China.
  • 2. National Protein Science Technology Center, Tsinghua University, 100084 Beijing, China.
  • 3. MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, 100084 Beijing, China.
  • 4. MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China. Electronic address: [email protected].
PMID: 31230984 DOI: 10.1016/j.cmet.2019.05.022
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.

Keywords
OLFR734; asprosin; cAMP; gluconeogenesis.
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