GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects
Da Young Oh,1,4 Saswata Talukdar,1,4 Eun Ju Bae,1 Takeshi Imamura,2 Hidetaka Morinaga,1 WuQiang Fan,1 Pingping Li,1 Wendell J. Lu,1 Steven M. Watkins,3 and Jerrold M. Olefsky1,*1Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA 2Division of Pharmacology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu-city, Shiga, 520-2192 Japan 3Tethys Bioscience, 3410 Industrial Boulevard, Suite 103, West Sacramento, CA 95691, USA 4These authors contributed equally to this work *Correspondence: jolefsky@ucsd.edu
DOI 10.1016/j.cell.2010.07.041
SUMMARY
Omega-3 fatty acids (u-3 FAs), DHA and EPA, exert anti-inflammatory effects, but the mechanisms are poorly understood. Here, we show that the G protein-coupled receptor 120 (GPR120) functions as an u-3 FA receptor/sensor. Stimulation of GPR120 with u-3 FAs or a chemical agonist causes broad anti-inflammatory effects in monocytic RAW 264.7 cells and in primary intraperitoneal macrophages.
All of these effects are abrogated by GPR120 knockdown.
Since chronic macrophage-mediated tissue inflammation is a key mechanism for insulin resistancein obesity, we fed obese WT and GPR120 knockout mice a high-fat diet with or without u-3 FA supplementation. The u-3 FA treatment inhibited inflammation and enhanced systemic insulin sensitivity in WT mice, but was without effect in GPR120 knockout mice. In conclusion, GPR120 is a functional u-3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation.
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