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Omega-3s Show New Anti-Inflammatory Ability
10/7/2010
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by Craig Weatherby


Omega-3 fatty acids from fish are the same omega-3s proven essential to human immune functions, including inflammation control.
 
In particular, the omega-3 known as EPA has been associated with mild anti-inflammatory effects, but it’s never been fully clear how it moderates inflammation.
 
It’s been thought that omega-3s primarily exert their anti-inflammatory effects through their role as precursors to immune-system chemicals called eicosanoids (eye-cose-uh-noyds), which were made famous by Dr. Barry Sears’ “Zone” diet books.
 
But new findings from the University of California, San Diego suggest an important new way in which omega-3s moderate inflammation.
 
And the new animal study also indicates that omega-3s can enhance insulin sensitivity… the same effect produced by diabetes drugs such as Avandia.
 
Chronic inflammation manifests in fat cells and promotes insulin resistance, which raises the risk of diabetes.
 
In humans and mice alike, inflammation is implemented in large part by immune system cells called macrophages, which were one focus of the researchers’ omega-3 experiment.
 
Study focuses on cells linked to inflammation and diabetes
A group of scientists from the University of California conducted a study in mice that lack the gene needed to produce a cell-surface receptor called GPR120 (Oh da Y et al. 2010).
 
GPR120 is involved in inflammation and insulin sensitivity, which explains why this cell receptor is the target of glitizar-class diabetes drugs such as Avandia.
 
The UC San Diego team knew from previous research that omega-3s are uniquely potent activators of GPR120 on the surfaces of macrophage cells and mature fat cells (adipocytes) alike (Burns RN et al. 2010).
 
The UC team focused on GPR120 precisely because it occurs on the surfaces of macrophage and adipocytes, where inflammation manifests and begins to degrade insulin sensitivity, leading to diabetes.
 
Accordingly, the researchers used so-called GPR120 “knock-out” mice to see whether omega-3s could trigger anti-inflammatory and insulin sensitizing effects without working through this cell receptor.
 
Mice lacking GPR120 receptor got no omega-3 benefit
When GPR120 knock-out mice were fed a high-fat diet that included omega-3 fatty acids, they developed inflammation and insulin resistance.
 
In contrast, while normal mice fed the same high-fat diet gained weight, the omega-3s in their diet exerted broad, robust anti-inflammatory effects.
 
And the researchers were surprised to see that activation of GPR120 by omega-3s blocked all of the known pro-inflammatory pathways.
 
The dietary omega-3s were also as or more effective than the insulin-sensitizing diabetes drug Avandia (rosiglitazone), which has been the subject of concern regarding increased cardiovascular risks.
 
In addition, the UC team reported that dietary omega-3s blocked the migration of pro-inflammatory macrophage cells into tissues, which they called “a remarkable effect.”
 
These findings may or may not apply to humans, and it is too early to draw any firm conclusions.
 
And omega-3s display a relatively low affinity for the GPR120 receptor, so it is possible that other natural or synthetic molecules might work even better.
 
 
Sources
  • Burns RN, Moniri NH. Agonism with the omega-3 fatty acids alpha-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor. Biochem Biophys Res Commun. 2010 Jun 11;396(4):1030-5. Epub 2010 May 13.
  • González-Périz A, Horrillo R, Ferré N, Gronert K, Dong B, Morán-Salvador E, Titos E, Martínez-Clemente M, López-Parra M, Arroyo V, Clària J. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J. 2009 Jun;23(6):1946-57. Epub 2009 Feb 11.
  • Kuda O, Jelenik T, Jilkova Z, Flachs P, Rossmeisl M, Hensler M, Kazdova L, Ogston N, Baranowski M, Gorski J, Janovska P, Kus V, Polak J, Mohamed-Ali V, Burcelin R, Cinti S, Bryhn M, Kopecky J. n-3 fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet. Diabetologia. 2009 May;52(5):941-51. Epub 2009 Mar 11. Erratum in: Diabetologia. 2009 Jul;52(7):1455.
  • Oh da Y, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, Olefsky JM. GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects. Cell. 2010 Sep 3;142(5):687-98.
  • Rasic-Milutinovic Z, Perunicic G, Pljesa S, Gluvic Z, Sobajic S, Djuric I, Ristic D. Effects of N-3 PUFAs supplementation on insulin resistance and inflammatory biomarkers in hemodialysis patients. Ren Fail. 2007;29(3):321-9.
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