Volume 33, No 8, Aug 2023

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 33 Issue 8, August 2023: 644-647

LETTERS TO THE EDITOR

Structural basis of omega-3 fatty acid receptor FFAR4 activation and G protein coupling selectivity

Han Yin¹ , Asuka Inoue² , Zhengxiong Ma¹ , Xinyan Zhu¹ , Ruixue Xia¹ , Zhenmei Xu¹ , Na Wang¹ , Yaning Duan¹ , Anqi Zhang¹ , Changyou Guo¹ , Yuanzheng He^1,*

¹Laboratory of Receptor Structure and Signaling, HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, China
²Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, Japan
Correspondence: Yuanzheng He(ajian.he@hit.edu.cn)

Dear Editor,

Omega (ω)-3 fatty acids are known to have multiple beneficial effects on health, including anti-inflammation, enhancement of glucose uptake and promotion of brain development.1 The effects of ω-3 fatty acids are mainly mediated by free fatty acid receptor 4 (FFAR4, also known as GPR120), a member of G protein-coupled receptor (GPCR) superfamily. FFAR4 plays crucial roles in maintaining metabolic homeostasis via regulating adipogenesis, insulin sensitivity and inflammation, and is a highly valuable target for treating metabolic diseases such as diabetes. Other FFARs include FFAR1 (GPR40) which responds to long-chain FFAs (> 12 carbons), and FFAR2 (GPR43) and FFAR3 (GPR41) that respond to short-chain FFAs (< 6 carbons). FFAR4 responds to long-chain FFAs, and a common feature of FFAR4 ligands is the existence of multiple cis double-bonds on the acyl chain of the fatty acids, such as α-linolenic acid (18:3, aLa), stearidonic acid (18:4), eicosapentaenoic acid (20:5, EPA) and docosahexaenoic acid (22:6, DHA).1 FFAR4 primarily couples to Gq pathway, but also has been reported to signal through Gs and Gi.1

https://doi.org/10.1038/s41422-023-00835-x

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