Fish oil has been used as an anti-inflammatory (and a lot of other things) but scientists haven't been sure how the omega-3 fatty acids in fish oil work in that capacity but a new report in Cell shows how omega-3 fatty acids both shut down inflammation and reverse diabetes in obese mice.   The report says omega-3s alleviate inflammation by acting on a receptor (GPR120) found in fat tissue and on inflammatory immune cells called macrophages, studies in mice show.

GPR120 is a G protein-coupled receptor (GPCRs), a group involved in many important cell functions and that includes the targets of many drugs. Other researchers had recently shown that five orphan GPCRs, GPR120 included, respond to free fatty acids.

"Omega-3s are very potent activators of GPR120 on macrophages -- more potent than any other anti-inflammatory we've ever seen," said Jerrold Olefsky of the University of California, San Diego.  There are all sorts of ways to trigger inflammation, he added. Activation of GPR120 by omega-3s blocks not one, but all inflammatory pathways.

Olefsky's team focused on GPR120 from the start because it turned up in fat tissue and on macrophages. If your goal is to fight inflammation, "that's just where you'd want them to be expressed," Olefsky said. 

Once they knew how omega-3s were working through GPR120, the researchers looked to a mouse that lacked the receptor. When those animals were made obese on 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; the omega-3s didn't help at all. Normal mice on a high-fat diet of course still gained weight, but omega-3s "had a really robust effect in preventing inflammation," Olefsky said. That anti-inflammatory effect acted as an insulin sensitizer, and a pretty good one at that. The omega-3 treatment was as effective, or even more effective, than the popular insulin-sensitizing drug Rosiglitazone (trade name Avandia).

Olefsky said the dose of omega-3 it took to get these effects in the mice was enough to double their blood concentrations. "That's a big increase," he said, "but not unbelievable."

What any of this means for humans isn't 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 for some indications. Olefsky isn't going to make any recommendation at this point, but says he doesn't see much of a downside to taking the supplements "as long as it isn't in enormous doses."

There are more details the researchers hope to work out. For one, omega-3s seem to block the migration of macrophage cells into body tissues. "It's a remarkable effect, and we don't know its action," he said.

While omega-3s appear to be very good at what they do in activating GPR120 to curb inflammation, it's possible that a small molecule could be found to work even better, Olefsky said, noting that omega-3 has a relatively low affinity for the receptor.

One interesting tidbit that Olefsky says even many scientists don't know: Like us, fish don't actually produce omega-3 fatty acids very efficiently at all. Instead, they become enriched with the fatty acids by eating algae.

Citation: 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, Volume 142, Issue 5, 687-698, 3 September 2010 DOI 10.1016/j.cell.2010.07.041