Format

Send to

Choose Destination
J Lipid Res. 2014 Jun;55(6):1150-64. doi: 10.1194/jlr.M047357. Epub 2014 Mar 16.

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway.

Author information

1
Max Delbrueck Center for Molecular Medicine, Berlin, Germany Experimental and Clinical Research Center (ECRC), Berlin, Germany.
2
Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
3
Experimental and Clinical Research Center (ECRC), Berlin, Germany.
4
Humboldt University of Berlin, Berlin, Germany.
5
Omegametrix GmbH, Martinsried, Germany.
6
Experimental and Clinical Research Center (ECRC), Berlin, Germany HELIOS Klinikum Berlin-Buch, Berlin, Germany.
7
Lipidomix GmbH, Berlin, Germany.

Abstract

Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) contribute to the regulation of cardiovascular function. CYP enzymes also accept EPA and DHA to yield more potent vasodilatory and potentially anti-arrhythmic metabolites, suggesting that the endogenous CYP-eicosanoid profile can be favorably shifted by dietary omega-3 fatty acids. To test this hypothesis, 20 healthy volunteers were treated with an EPA/DHA supplement and analyzed for concomitant changes in the circulatory and urinary levels of AA-, EPA-, and DHA-derived metabolites produced by the cyclooxygenase-, lipoxygenase (LOX)-, and CYP-dependent pathways. Raising the Omega-3 Index from about four to eight primarily resulted in a large increase of EPA-derived CYP-dependent epoxy-metabolites followed by increases of EPA- and DHA-derived LOX-dependent monohydroxy-metabolites including the precursors of the resolvin E and D families; resolvins themselves were not detected. The metabolite/precursor fatty acid ratios indicated that CYP epoxygenases metabolized EPA with an 8.6-fold higher efficiency and DHA with a 2.2-fold higher efficiency than AA. Effects on leukotriene, prostaglandin E, prostacyclin, and thromboxane formation remained rather weak. We propose that CYP-dependent epoxy-metabolites of EPA and DHA may function as mediators of the vasodilatory and cardioprotective effects of omega-3 fatty acids and could serve as biomarkers in clinical studies investigating the cardiovascular effects of EPA/DHA supplementation.

KEYWORDS:

cytochrome P450; lipidomics; nutrition

PMID:
24634501
PMCID:
PMC4031946
DOI:
10.1194/jlr.M047357
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center