Omega-3 Fatty Acids Block Macrophage Inflammatory Action

GPR120, which is limited to fat tissue and macrophages, is a member of a large protein family many of whose members are drug targets.

The investigators reported in the September 3, 2010, issue of the journal Cell that the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) bind to and activate GPR120. Activated GPR120 triggers a molecular pathway that blocks the macrophages' inflammatory role.

They fed obese mice and mice genetically engineered to lack the gene for GPR120 (GPR120 knockout mice) a high fat diet with or without omega-3 fatty acid supplementation. The omega-3 treatment inhibited inflammation and enhanced systemic insulin sensitivity in the obese mice, but was without effect in GPR120 knockout mice.

"It is just an incredibly potent effect,” said senior author Dr. Jerrol Olefsky, professor of medicine at the University of California, San Diego. "The omega-3 fatty acids switch on the receptor, killing the inflammatory response. The receptor evolved to respond to a natural product – omega-3 fatty acids – so that the inflammatory process can be controlled. Our work shows how fish oils safely do this, and suggests a possible way to treating the serious problems of inflammation in obesity and in conditions like diabetes, cancer, and cardiovascular disease through simple dietary supplementation.”

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University of California, San Diego