Cited by 2,428Fatty Acid Research and HealthAdipokines, Inflammation, and Metabolic DiseasesPeroxisome Proliferator-Activated Receptors

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

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Oh, Da Young, Talukdar, Saswata, Bae, Eun Ju, Imamura, Takeshi, Morinaga, Hidetaka, Fan, WuQiang, Li, Pingping, Lu, Wendell J., Watkins, Steven M., Olefsky, Jerrold M.·2010·Cell

DOI 10.1016/j.cell.2010.07.041PMC PMC2956412

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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.

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A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
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Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance
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Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120
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Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40
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“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 u-3 FA supplementation.”
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Influential
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Authors: Oh, D. Y., Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W. J., Watkins, S. M., & Olefsky, J. M.
Affiliations: University of California San Diego (US)
Shiga University of Medical Science (JP)
Corresponding author: Olefsky, Jerrold M.
ORCID: Oh, Da Young
Talukdar, Saswata
Bae, Eun Ju
Morinaga, Hidetaka
Fan, WuQiang
Li, Pingping
Watkins, Steven M.
Olefsky, Jerrold M.
Venue: Cell
Publisher: Elsevier BV
Published: 2010-09
Volume: 142
Issue: 5
Pages: 687-698
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2010.07.041
PMC: PMC2956412
OpenAlex: W2131094572
Cited by: 2,428
References: 49
Citations by year: 2026: 97 · 2025: 134 · 2024: 123 · 2023: 129 · 2022: 134 · 2021: 180 · 2020: 172 · 2019: 157 · 2018: 158 · 2017: 181 · 2016: 197 · 2015: 177 · 2014: 165 · 2013: 162 · 2012: 143
FWCI: 127.77
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1081 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (NIDDK DK033651, DK 074868, DK063491, U54 HD 012303-25)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: GPR120, docosahexaenoic acid, eicosapentaenoic acid, anti-inflammatory activity, insulin sensitivity, insulin resistance, macrophage inflammation, obesity, high-fat diet, G protein-coupled receptors, RAW 264.7 macrophages
MeSH terms: Animals, Anti-Inflammatory Agents, Cell Line, Dietary Fats, Humans, Hypoglycemic Agents, Insulin Resistance, Macrophages, Obesity, Fatty Acids, Omega-3, Mice, Knockout, Dietary Supplements, 3T3-L1 Cells, Receptors, G-Protein-Coupled, Mice

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

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