Omega-3 and omega-6 PUFAs induce the same GPR120-mediated signalling events, but with different kinetics and intensity in Caco-2 cells

Lipids Health Dis. 2013 Jul 13:12:101. doi: 10.1186/1476-511X-12-101.


Background: Omega-3 PUFAs are known to have anti-inflammatory properties, and different mechanisms are involved. GPR120 is a G-protein coupled receptor that has recently received attention because of its anti-inflammatory signalling properties after binding omega-3 PUFAs. However, both omega-3 and omega-6 PUFAs are natural GPR120 ligands. The aim of this study was to study possible differences in GPR120-mediated signalling events after treatment with different long-chain PUFAs in intestinal epithelial cells. We also investigated possible GPR120-mediated anti-inflammatory effects of different long-chain PUFAs that may be relevant in the understanding of how dietary PUFAs influence inflammatory responses in inflammatory diseases such as IBD.

Methods: We used Caco-2 cells as a model system to study GPR120-mediated signalling events because we found this cell line to express GPR120, but not GPR40, another plasma membrane receptor for medium- and long chain fatty acids. Increase in cytosolic Ca2+concentration, activation of MAP kinase ERK1/2 and the inhibition of IL-1β induced NF-κB activity were studied to reveal potential differences in the activation of GPR120 by the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the omega-6 PUFA arachidonic acid (AA).

Results: We found that EPA, DHA and AA enhanced the cytosolic concentration of the second messenger Ca2+ with the same efficiency, but with different kinetics. Both omega-3 and omega-6 PUFAs activated MAP kinase ERK1/2, but differences regarding kinetics and intensity were also observed in this pathway. ERK1/2 activation was shown to be dependent upon EGFR and Raf-1. We further investigated the ability of EPA, DHA and AA to inhibit NF-κB activity in Caco-2 cells. All PUFAs tested were able to inhibit IL-1β induced breakdown of IκBα after binding to GPR120, but with different potency.

Conclusions: Our results show that EPA, DHA and AA elicit the same signalling events, but with different kinetics and efficiency through GPR120 in Caco-2 cells. We show, for the first time, that both omega-3 and omega-6 PUFAs inhibit NF-κB activation in intestinal epithelial cells. Our results may be important for understanding how dietary PUFAs influence inflammatory processes relevant in delineating effects of PUFAs in the treatment of IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage
  • Arachidonic Acid / metabolism
  • Caco-2 Cells
  • Calcium Signaling
  • Cytosol / metabolism
  • Docosahexaenoic Acids / metabolism
  • Eicosapentaenoic Acid / metabolism
  • Fatty Acids, Omega-3* / administration & dosage
  • Fatty Acids, Omega-3* / metabolism
  • Fatty Acids, Omega-6* / administration & dosage
  • Fatty Acids, Omega-6* / metabolism
  • Fatty Acids, Unsaturated / administration & dosage
  • Fatty Acids, Unsaturated / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Interleukin-1beta / metabolism
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NF-kappa B / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction


  • Anti-Inflammatory Agents
  • FFAR4 protein, human
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • Receptors, G-Protein-Coupled
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Eicosapentaenoic Acid
  • Mitogen-Activated Protein Kinase Kinases