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Edited* by Michael Karin, School of Medicine, University of California at San Diego, La Jolla, CA, and approved April 18, 2012 (received for review January 15, 2012)
Abstract
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.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: edennis{at}ucsd.edu.
Author contributions: P.C.N. and E.A.D. designed research; P.C.N. performed research; P.C.N. analyzed data; and P.C.N. and E.A.D. wrote the paper.
The authors declare no conflict of interest.
↵*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1200189109/-/DCSupplemental.
ω3 fatty acid effects on eicosanoid metabolism
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