Omega-3s anti-inflammatory mechanism revealed
The new research published in the journal Cell, suggests the mechanisms behind omega-3’s actions as an anti-onflammatory are due to its action on G-protein-coupled receptor 120 (GPR120) working as an omega-3 FA receptor/sensor.
"Omega-3s are very potent activators of GPR120 on macrophages - more potent than any other anti-inflammatory we've ever seen," said lead researcher Dr Jerrold Olefsky of the University of California, San Diego.
Omega-3 fatty acids have been long associated with anti-inflammatory effects; however the mechanisms behind such effects have been poorly understood.
GPR120 is a G protein-coupled receptor (GPCRs) - part of a group involved in many important cell functions, and is the target of many drugs.
Previous research has suggested that five GPCRs – including GPR120 included – respond well respond to free fatty acids.
Since chronic tissue inflammation is linked to insulin resistance in obesity, the researchers used GPR120 knock-out mice to investigate if omega-3 leads to GPR120-mediated anti-inflammatory and insulin sensitizing effects in vivo.
Researchers found that GPR120 functions as an omega-3 receptor in pro-inflammatory macrophages and mature adipocytes.
When knock-out mice 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.
The study also observed that by signalling through GPR120, omega-3 fatty acids mediate potent anti-inflammatory effects to inhibit certain key inflammatory signaling pathways.
The study reports that omega-3 treatment was as effective - or in some cases more effective - than the popular insulin-sensitizing drug Rosiglitazone.
The researchers noted that activation of GPR120 by omega-3s blocks not one, but all inflammatory pathways.
Olefsky said his team focused on GPR120 from the beginning because of where it is found - in fat tissue and on macrophages. Olefsky noted that if your goal is to fight inflammation then "that's just where you'd want them to be expressed."
How these findings can be interpreted for humans is not yet clear, but with a growing trend in omega-3 supplementation and increased dietary intakes of omega-3 a goal for many consumers.
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."
Olefski said that further research needs to be conducted into several – currently unknown - omega-3 mechanisms. For one, omega-3s seems to block the migration of macrophage cells into tissues - "It's a remarkable effect, and we don't know its action," he added.
The researchers also pointed out that whilst omega-3s appear to be very good at activating GPR120 to reduce inflammation, the fatty acid actually has a relatively low affinity for the receptor. Olefsky commented that it is possible other small molecules could be found to work even better than omega-3.
Vol 142(5) pp. 687 – 698, doi: 10.1016/j.cell.2010.07.041
“GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects”
Authors: D.Y. Oh, S. Talukdar, E. J. Bae, T. Imamura, H. Morinaga, W.Q. Fan, P. Li, W.J. Lu, S.M. Watkins, J.M. Olefsky