GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects

Dayoung Oh, Saswata Talukdar, Eun Ju Bae, Takeshi Imamura, Hidetaka Morinaga, Wu Qiang Fan, Pingping Li, Wendell J. Lu, Steven M. Watkins, Jerrold M. Olefsky

Research output: Contribution to journalArticle

1304 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)687-698
Number of pages12
JournalCell
Volume142
Issue number5
DOIs
StatePublished - Sep 3 2010

    Fingerprint

Keywords

  • Humdisease
  • Signaling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Oh, D., Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., Fan, W. Q., Li, P., Lu, W. J., Watkins, S. M., & Olefsky, J. M. (2010). GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects. Cell, 142(5), 687-698. https://doi.org/10.1016/j.cell.2010.07.041