Tuesday, September 7, 2010

How Fish Oils Work Against Inflammation and Diabetes

Omega-3 fatty acids have been long associated with anti-inflammatory effects; however the mechanisms behind such effects have been poorly understood.

Jerrold Olefsky, MD, and colleagues at the University of California, San Diego School of Medicine have recently identified the molecular mechanism that involves activation of G-protein receptor called GPR120 in macrophages.

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.

Obesity and diabetes are closely correlated. 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 GPR120 receptor is found only on pro-inflammatory macrophages in mature fat cells. The researchers used GPR120 knock-out mice to investigate if omega-3 leads to GPR120-mediated anti-inflammatory and insulin sensitizing effects in vivo.

When knock-out mice, mice without GPR 120 receptors, were fed a high-fat diet and treated with omega-3 fatty acids, they showed all the signs of inflammation and the insulin resistance that leads to diabetes with omega-3 having no effect. Normal mice on a high-fat diet still gained weight, however, omega-3s "had a really robust effect in preventing inflammation," Olefsky said.

How these findings can be interpreted for humans is not yet clear, but a large number of people are already supplementing their diets with fish oil and an omega-3 prescription drug is already on the market as an adjunct treatment for severe hypertriglyceridemia.

Olefski says it is too early to make any formal reccomendations at the moment, but highlights that he does not see any problem with people taking omega-3 supplementations "as long as it isn't in enormous doses."

Journal Reference:

Da Young Oh, Saswata Talukdar, Eun Ju Bae, Takeshi Imamura, Hidetaka Morinaga, WuQiang Fan, Pingping Li, Wendell J. Lu, Steven M. Watkins, Jerrold M. Olefsky. GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects. Cell, 2010; 142 (5): 687-698

What is a knockout mouse?

A knockout mouse is a laboratory mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA. The loss of gene activity often causes changes in a mouse's phenotype, which includes appearance, behavior and other observable physical and biochemical characteristics.

Knocking out the activity of a gene provides valuable clues about what that gene normally does. Humans share many genes with mice. Consequently, observing the characteristics of knockout mice gives researchers information that can be used to better understand how a similar gene may cause or contribute to disease in humans.
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