GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects
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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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The anti-inflammatory effects of omega-3 fatty acids seem to be mediated by binding to the G-protein-coupled receptor 120 and inhibition of NLRP3 inflammasome activity.
“The anti-inflammatory effects of omega-3 fatty acids seems to be mediated by binding to the G-protein–coupled receptor 120 and inhibition of NLRP3 inflammasome activity (53,54).”
From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [53]
In macrophages and adipocytes, the G-protein coupled receptor GPR120 is an omega-3 sensitive receptor that exhibits anti-inflammatory properties through the suppression of TNF-activation.
“in macrophages and adipocytes the G-protein coupled receptor GPR120 is an omega-3 sensitive receptor that exhibits anti-inflammatory properties through the suppression of TNF-activation [141]”
From Omega-3 Fatty Acids and Skeletal Muscle Health (2015) · cites this paper as [141]
GPR120 expression is negligible in skeletal muscle and would therefore not explain the changes induced by omega-3 PUFAs in tissue culture models.
“GPR120 expression is negligible in skeletal muscle and would therefore not explain the changes induced by omega-3 PUFAs in tissue culture models [141]”
From Omega-3 Fatty Acids and Skeletal Muscle Health (2015) · cites this paper as [141]
n-3 PUFAs EPA and DHA can reduce inflammation via incorporation into membrane phospholipids, inhibiting production of pro-inflammatory eicosanoids and reducing activation of immune cells and release of pro-inflammatory cytokines.
“In summary, the n-3 PUFAs EPA and DHA can reduce inflammation via their incorporation into membrane phospholipids, where they inhibit the production of pro-inflammatory eicosanoids, reducing of activation of immune cells and the associated release of pro-inflammatory cytokines [71,97,98].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [98]
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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
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 142
- Issue
- 5
- Pages
- 687-698
- ISSN
- 0092-8674 (ISSN-L)
- 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
- 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 › Epidemiology › 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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