title: GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects.
abstract: Omega-3 fatty acids (omega-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 omega-3 FA receptor/sensor. Stimulation of GPR120 with omega-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 omega-3 FA supplementation. The omega-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 omega-3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Da Young
authors.initials: DY
authors.lastname: Oh
authors.forename: Saswata
authors.initials: S
authors.lastname: Talukdar
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Bae
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imamura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Morinaga
authors.forename: WuQiang
authors.initials: W
authors.lastname: Fan
authors.forename: Pingping
authors.initials: P
authors.lastname: Li
authors.forename: Wendell J
authors.initials: WJ
authors.lastname: Lu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Watkins
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Olefsky
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism; D002460:Cell Line; D004041:Dietary Fats / Q000378:metabolism; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism; D007333:Insulin Resistance; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D004041:Dietary Fats; C498007:FFAR4 protein, mouse; D015525:Fatty Acids, Omega-3; D007004:Hypoglycemic Agents; D043562:Receptors, G-Protein-Coupled
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