@article{062ab6e1ea8d478a9b72fbc0b6973e1e,
title = "GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects",
abstract = "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.",
keywords = "Humdisease, Signaling",
author = "Dayoung Oh and Saswata Talukdar and Bae, {Eun Ju} and Takeshi Imamura and Hidetaka Morinaga and Fan, {Wu Qiang} and Pingping Li and Lu, {Wendell J.} and Watkins, {Steven M.} and Olefsky, {Jerrold M.}",
note = "Funding Information: We thank Jachelle M. Ofrecio and Sarah Nalbandian for their help with animal maintenance and Elizabeth J. Hansen for editorial assistance. We are grateful to Dr. Robert Lefkowitz (Howard Hughes Medical Institute, Duke University) for the gift of FLAG-tagged serial mutant β-arrestin2 constructs and to Dr. Maziyar Saberi at NGM Bio Inc. (San Francisco, CA) for GLP-1 measurements. We thank the Flow Cytometry Resource and Neal Sekiya for assistance with FACS analysis at the VA San Diego hospital, the UCSD Histology Core lab for technical help with processing liver specimens, and UCSD Microscope Resource for microscopy analysis. This study was funded in part by the National Institutes of Health grants NIDDK DK033651 (J.M.O.), DK063491 (J.M.O.), DK 074868 (J.M.O.), and the Eunice Kennedy Shriver NICHD/NIH through a cooperative agreement U54 HD 012303-25 as part of the specialized Cooperative Centers Program in Reproduction and Infertility Research. ",
year = "2010",
month = sep,
day = "3",
doi = "10.1016/j.cell.2010.07.041",
language = "English (US)",
volume = "142",
pages = "687--698",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}