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Old 09-03-2010, 08:56 AM
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Default Omega-3s anti-inflammatory mechanism revealed

Omega-3s may reduce inflammation by acting on a receptor found in fat tissue and on inflammatory immune cells called macrophages, according to research.




The new research published in the journal Cell, suggests the mechanisms behind omega-3s 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.
Anti-inflammatory
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.
Robust effect
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.
Interpretation
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.



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Old 09-03-2010, 12:09 PM
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You can read the full text of the paper here
Here is a quote from the conclusion section.
Quote:
n summary, we have found that GPR120 functions as an ω-3 FA receptor/sensor and mediates robust and broad anti-inflammatory effects, particularly in macrophages.
After ligand stimulation, GPR120 couples to β-arrestin2 which is followed by receptor endocytosis and inhibition of TAB1-mediated activation of TAK1, providing a mechanism for inhibition of both the TLR and TNF-α proinflammatory signaling pathways.
Since chronic tissue inflammation is linked to insulin resistance in obesity, we used GPR120 KO mice to demonstrate that ω-3 FAs cause GPR120-mediated anti-inflammatory and insulin sensitizing effects in vivo.
Overall, these results strongly argue that anti-inflammatory effects can ameliorate insulin resistance in obesity.
Taken together, GPR120 emerges as an important control point in the integration of anti-inflammatory and insulin sensitizing responses, which may prove useful in the future development of new therapeutic approaches for the treatment of insulin resistant diseases.
Just typical of modern medical research.

They identify the means by which omega 3 helps maintain insulin sensitivity.

Then rather than suggesting effective supplement levels to raise omega 3 status and explaining how omega 6 levels neutralise the impact of omega 3 when omega 6 levels are too high in relation to omega 3 intake, they totally ignore the cheapest most direct way of ensuring tissue levels of omega 3 are improved, and go straight for future development of new therapeutic approaches for the treatment of insulin resistant diseases That's where the money is.

Who is interested in disease prevention while there is more money to be made from treating disease after it's diagnosed?

Remember the half life of omega 6 in the body is around 2 yrs so it's a long term project to ensure omega 3 levels are kept high throughout the time you are waiting for the effects of eliminating omega 6 industrial vegetable oils to occur.
Using at least 2000 mg per day of EPA + DHA should be sufficient.
I take a couple of teaspoons of this Nature's Answer, Liquid Omega-3, Deep Sea Fish Oil EPA/DHA, Natural Orange Flavor, 16 fl oz (480 ml)$14.95
If you prefer capsules then THREE of these daily (one with each meal) would also be sufficient.
Code WAB666 saves $5 for new IHERB users.
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Old 09-03-2010, 01:48 PM
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Thanks Ted. I assumed the nutra-ingredients site had presented the whole topic. I thought they were reporting a newly discovered pathway, without conclusive evidence on how it would translate to human reactions, off a possible new drug. We are still going to buy omega-3 supplements based on so much other evidence.

"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,...."
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