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Discovery of omega-3 fatty acid molecular mechanism paves way for development of dietary remedy for diabetes

Published on September 3, 2010 at 2:07 AM · No Comments

Researchers at the University of California, San Diego School of Medicine have identified the molecular mechanism that makes omega-3 fatty acids so effective in reducing chronic inflammation and insulin resistance.

The discovery could lead to development of a simple dietary remedy for many of the more than 23 million Americans suffering from diabetes and other conditions.

Writing in the advance online edition of the September 3 issue of the journal Cell, Jerrold Olefsky, MD, and colleagues identified a key receptor on macrophages abundantly found in obese body fat. Obesity and diabetes are closely correlated. The scientists say omega-3 fatty acids activate this macrophage receptor, resulting in broad anti-inflammatory effects and improved systemic insulin sensitivity.

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.

Olefsky and colleagues looked at cellular receptors known to respond to fatty acids. They eventually narrowed their focus to a G-protein receptor called GPR120, one of a family of signaling molecules 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.

"It's just an incredibly potent effect," said Olefsky, a professor of medicine and associate dean of scientific affairs for the UC San Diego School of Medicine. "The omega-3 fatty acids switch on the receptor, killing the inflammatory response."

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