Fish oil is touted for its anti-inflammatory and anti-diabetic benefits, but scientist weren't sure how the omega-3 fatty acids in fish oil work. Now, according to a report in the September 3rd issue of the journal Cell, scientists have nailed how omega-3 fatty acids both shut down inflammation and reverse diabetes in obese mice.
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.
"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.
In fact, there are all sorts of ways to trigger inflammation, he added. Activation of GPR120 by omega-3s blocks not one, but all inflammatory pathways.
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.
Olefsky's team focused on GPR120 from the start because of where 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.
The researchers include Da Young Oh, University of California, San Diego, La Jolla, CA; Saswata Talukdar, University of California, San Diego, La Jolla, CA; Eun Ju Bae, University of California, San Diego, La Jolla, CA; Takeshi Imamura, Shiga University of Medical Science, Tsukinowa, Seta, Otsu-city, Shiga, Japan; Hidetaka Morinaga, University of California, San Diego, La Jolla, CA; WuQiang Fan, University of California, San Diego, La Jolla, CA; Pingping Li, University of California, San Diego, La Jolla, CA; Wendell J. Lu, University of California, San Diego, La Jolla, CA; Steven M. Watkins, Tethys Bioscience, West Sacramento, CA; and Jerrold M. Olefsky, University of California, San Diego, La Jolla, CA.
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