Cell
Volume 142, Issue 5, 3 September 2010, Pages 687-698
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Article
GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects

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Summary

Omega-3 fatty acids (ω-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 ω-3 FA receptor/sensor. Stimulation of GPR120 with ω-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 resistance in obesity, we fed obese WT and GPR120 knockout mice a high-fat diet with or without ω-3 FA supplementation. The ω-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 ω-3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation.

Highlights

► GPR120 is expressed in macrophages and Kupffer cells and is induced in obesity ► GPR120 functions as an omega 3 fatty acid (ω-3 FA) receptor/sensor ► ω-3 FAs exert broad anti-inflammatory effects through GPR120 in macrophages ► GP120 mediates insulin sensitization by ω-3 FAs in obese mice

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These authors contributed equally to this work