Oh et al. Cell 142 (3 September 2010)

Good fish. Fat tissue taken from mice on a high-fat diet rich in omega-3 fatty acids (right) has fewer inflammatory immune cells (shown in green) than fat tissue taken from mice that did not receive the omega-3 supplement (left).

How Fish Oil Fights Inflammation

Pass the bass, please. Omega-3 fatty acids, a main component of fish oil, have a reputation as potent anti-inflammatory agents. Now researchers think they know how the acids block this immune response. They've also found that omega-3s can help fight diabetes in obese mice, pointing the way to potential therapies in humans.

To understand how omega-3s curb inflammation, Jerrold Olefsky, an endocrinologist at the University of California, San Diego, and his colleagues trawled through the data on a family of proteins called G protein-coupled receptors, which can bind to a number of different fatty acids. One of these receptors—GPR120—"jumped right out," Olefsky says. Olefsky's group found it on immune cells involved in inflammation, as well as in mature fat cells, and they noted that it seemed to bind to omega-3s.

To confirm the link, the team doused GPR120-containing mouse immune cells with omega-3 fatty acids. That "shut down almost all of the inflammatory pathways," Olefsky says. "It was a very powerful effect."

The researchers also genetically modified mice to lack the GPR120 receptor. They then fed the mutant mice and normal mice a high-fat diet. Both groups became obese and developed a mouse form of diabetes. Scientists have long suspected a link between inflammation and obesity-linked diabetes; and indeed, when Olefsky's team supplemented the fatty diet with a hefty helping of omega-3 fatty acids—enough to double the concentration of omega-3 in the mice's blood—the normal mice experienced a reduction in their diabetic symptoms. The rodents remained obese, but they regained some sensitivity to insulin, meaning they didn't need as much insulin to take up glucose and burn it to produce energy. In fact, the supplemented diet worked as well to combat insulin resistance as the common diabetes drug Avandia, the team reports in the 3 September issue of Cell. The mutant mice remained diabetic regardless of how many omega-3s they consumed, highlighting the importance of the GPR120 receptor.

"The results are preliminary but exciting," says Nader Moniri, a pharmacologist at Mercer University in Atlanta. "For the first time we're linking inflammation to GPR120." Moniri points out that the GPR120 receptor also shows up in intestinal cells, where it appears to regulate a hormone that prompts the pancreas to release insulin. That means there are two routes by which GPR120 could influence diabetes, which makes it a very nice drug target, he says.

Olefsky suggests that the GPR120 receptor is the main way by which omega-3s control inflammation, but he acknowledges that other mechanisms may exist. For example, digestion breaks down some omega-3s into shorter fatty acids. Some evidence suggests that these may also influence inflammation, though not through GPR120, he notes.

Olefsky also won't go so far as to recommend that anyone take fish oil pills to stave off inflammation or diabetes. "We've never worked with people on this," he says, "so we have no idea how much omega-3 fatty acids a person would have to take."

Posted in Biology, Health