Mechanism found for omega-3 fatty acids in reducing insulin resistance and inflammation
An article published in the September 3, 2010 issue of the journal Cell reports the discovery of researchers at the University of California, San Diego School of Medicine of the mechanism used by omega-3 fatty acids in lowering insulin resistance and chronic inflammation.
Recent research revealed that five members of a family of molecules known as G protein-coupled receptors respond to free fatty acids. Using cell cultures, Jerrold Olefsky, MD and colleagues found that exposure to omega-3 fatty acids activates one of these cellular receptors. The receptor, known as GPR120, is located on macrophages in mature fat cells and, when activated, prevents the macrophages from causing inflammation.
The researchers compared the effects of diets supplemented with the omega-3 fatty acids EPA and DHA in mice bred to lack the GPR120 receptor and normal mice. Prior to receiving EPA and DHA, both groups of animals received high fat diets for 15 weeks to induce obesity and insulin resistance. While the normal mice experienced enhanced insulin sensitivity and reduced inflammation after 5 weeks of omega-3 supplementation, mice lacking the receptor failed to benefit from the omega-3 fatty acids. The insulin-sensitizing ability of EPA and DHA was the same or greater than that found for the drug rosiglitazone in a separate group of normal obese mice.
"It's just an incredibly potent effect," enthused Dr Olefsky, who is 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."
"Omega-3s are very potent activators of GPR120 on macrophages -- more potent than any other anti-inflammatory we've ever seen," he remarked, adding that activation of GPR120 by omega-3 blocks all inflammatory pathways.
"This is nature at work," he observed. "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."
In the early stages of type 2 diabetes, insulin levels are already elevated (hyperinsulinemia). This is because the problem isn’t with insulin production; rather, the underlying defect in type 2 diabetes is a metabolic defect of insulin utilization. The delicate insulin receptors on cell membranes are less responsive to the insulin than are the insulin receptors of people without type 2 diabetes, which means that less glucose is absorbed from the blood stream than would be normally, and glucose levels slowly rise.
This elevation in glucose upsets the body’s natural balance, prompting the pancreas to discharge copious amounts of insulin to normalize glucose levels. This short-term, biological fix successfully drives glucose into cells, thereby lowering blood glucose levels, but it also hastens the disease’s progress. Eventually, the fragile insulin receptors become less sensitive (insulin resistant), which means that the pancreas must secrete even more insulin to keep clearing the blood of glucose. In later stages of the disease, the pancreas becomes “burned out” and can no longer produce adequate insulin. Insulin levels drop far below normal, allowing blood glucose to rise even higher and inflict greater damage.
In human experiments, omega-3 fatty acids lowered blood pressure and triglyceride levels, thereby relieving many of the complications associated with diabetes. In animals, omega-3 fatty acids cause less weight gain than other fats do; they have also been shown to have a neutral effect on LDL, while raising HDL and lowering triglycerides (Petersen M et al 2002).
Marine oil contains omega-3 fatty acids. The research on omega-3 fatty acids stems from studies of the Inuit (Eskimo) people, who seldom suffer from heart attacks even though their diets contain an enormous amount of fat from fish, seals, and whales, presumably because those sources of fat are very high in omega-3 fatty acids. Omega-3 fatty acids found in marine oil lower blood triglyceride levels, contribute to “thinning” the blood, and also decrease inflammation (Ebbesson SO et al 2005). These effects partially explain many of fish oil’s benefits.
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