Researchers investigating the function of a particular G-protein coupled receptor, GPR120, have found potent anti-inflammatory effects to be mediated when stimulated with ingredients of fish oil.
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are omega-3 fatty acids found in fish oil. These fatty acids have already been shown to have health benefits, e.g. DHA reduces blood triglycerides to decrease the risk of atherosclerosis and heart disease.
Chronic inflammation, mediated by macrophages (white blood cells that enter diseased tissues and mediate an inflammatory response), is linked to decreased sensitivity to insulin in obesity, thus the anti-inflammatory effects mediated upon GPR120 activation may promote insulin sensitisation.
Adipose (fat) tissue and pro-inflammatory tissue macrophages were found to express GPR120, and, in particular, the receptor was highly induced in the obese murine model. Further investigation by the research team found that DHA activation of GPR120 increased the translocation of GLUT4 (Glucose Transporter 4) to the cellular surface and hence transportation of glucose into the cells.
Monocytic cell lines and murine primary intraperitoneal macrophages both containing and lacking the GPR120 receptor were also used in the research. A high-fat diet with or without omega-3 fatty acid supplementation was fed to the mice, and in ordinary mice DHA and EPA mediated anti-inflammatory effects by inhibition of both the TLR (Toll-like Receptor) and TNF (Tumour Necrosis Factor) inflammatory pathways. In the GPR120 knockout mice DHA and EPA had no effect.
The research was led by Jerrold Olefsky, Associate Dean for Scientific Affairs and Professor of Medicine at University of California, San Diego School of Medicine. Speaking in video clips posted on the University of California’s website Prof. Olefsky said that potentially the effects seen in mice may be mediated in humans to treat insulin resistance. However, in experiments they had to give the mice relatively high doses of fatty acids, which would be non-beneficial to humans. Therefore it may be more reasonable to target GPR120 for therapeutic treatment. If they could find a small molecule that mimics the effects of the fatty acids then a reasonable dose may be consumed to mediate anti-inflammatory and anti-insulin resistance effects.
The researchers conclude that GPR120 may be an important signalling molecule in anti-inflammatory and insulin-sensitising responses thus may provide a new approach for the treatment of insulin resistant diseases.
Oh et al (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell, 142, 687-698.
The paper can be found at: