SAN DIEGO—Omega-3 fatty acids are effective in reducing chronic inflammation and insulin resistance because they activate a key receptor on body fat macrophages, according to researchers at the University of California, San Diego School of Medicine (10.1016/j.cell.2010.07.041). Activating this receptor results in broad anti-inflammatory effects and improved systemic insulin sensitivity.
Jerrold Olefsky, MD, and colleagues looked at cellular receptors known to respond to fatty acids, focusing on a G-protein receptor called GPR120, a signaling molecule involved in numerous cellular functions. The GPR120 receptor is found only on pro-inflammatory macrophages in mature fat cells. When the receptor is turned off, the macrophage produces inflammatory effects. But exposed to omega-3 fatty acids, specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the GPR120 receptor is activated and generates a strong anti-inflammatory effect.
“The omega-3 fatty acids switch on the receptor, killing the inflammatory response," said Olefsky, a professor of medicine and associate dean of scientific affairs for the UC San Diego School of Medicine, in a press release. “This is nature at work," said Olefsky. “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."
The scientists conducted their research using cell cultures and mice. Some of the mice were genetically modified to lack the GPR120 receptor. All of the mice were fed a high-fat diet with or without omega-3 fatty acid supplementation. The supplementation treatment inhibited inflammation and enhanced insulin sensitivity in ordinary obese mice, but had no effect in GPR120 knockout mice.
Macrophages are specialized white blood cells that engulf and digest cellular debris and pathogens. Part of this immune system response involves the macrophages secreting cytokines and other proteins that cause inflammation, a method for destroying cells and objects perceived to be harmful. Obese fat tissue contains lots of these macrophages producing lots of cytokines. The result can be chronic inflammation and rising insulin resistance in neighboring cells over-exposed to cytokines. Insulin resistance is the physical condition in which the natural hormone insulin becomes less effective at regulating blood sugar levels in the body, leading to myriad and often severe health problems, most notably type 2 diabetes mellitus.
The research is reported in the advance online edition of the September 3 issue of the journal Cell. Funding for this research came, in part, from a National Institutes of Health grant and the Eunice Kennedy Shriver NICHD/NIH.
