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Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling
Paul C. Norris and Edward A. Dennis
Proceedings of the National Academy of Sciences of the United States of America
Vol. 109, No. 22 (May 29, 2012), pp. 8517-8522
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/41602587
Page Count: 6
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Dietary fish oil containing ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), elicit cardioprotective and anti-inflammatory effects through unresolved mechanisms that may involve competition and inhibition at multiple levels. Here, we report the effects of arachidonic acid (AA), EPA, and DHA supplementation on membrane incorporation, phospholipase A₂ catalyzed release, and eicosanoid production in RAW264.7 macrophages. Using a targeted lipidomics approach, we observed that Toll-like receptor 4 and purinergic receptor activation of supplemented cells leads to the release of 22-carbon fatty acids that potently inhibit cyclooxygenase pathways. This inhibition was able to shunt metabolism of AA to lipoxygenase pathways, augmenting leukotriene and other lipoxygenase mediator synthesis. In resident peritoneal macrophages, docosapentaenoic acid (DPA) was responsible for cyclooxygenase inhibition after EPA supplementation, offering fresh insights into how EPA exerts anti-inflammatory effects indirectly through elongation to 22-carbon DPA.
Proceedings of the National Academy of Sciences of the United States of America © 2012 National Academy of Sciences