Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids

Christophe Morisseau, Bora Inceoglu, Kara Schmelzer, Hsing Ju Tsai, Steven L. Jinks, Christine M. Hegedus, Bruce D. Hammock

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

Beneficial physiological effects of long-chain n-3 polyunsaturated fatty acids are widely accepted but the mechanism(s) by which these fatty acids act remains unclear. Herein, we report the presence, distribution, and regulation of the levels of n-3 epoxy-fatty acids by soluble epoxide hydrolase (sEH) and a direct antinociceptive role of n-3 epoxy-fatty acids, specifically those originating from docosahexaenoic acid (DHA). The monoepoxides of the C18:1 to C22:6 fatty acids in both the n-6 and n-3 series were prepared and the individual regioisomers purified. The kinetic constants of the hydrolysis of the pure regioisomers by sEH were measured. Surprisingly, the best substrates are the mid-chain DHA epoxides. We also demonstrate that the DHA epoxides are present in considerable amounts in the rat central nervous system. Furthermore, using an animal model of pain associated with inflammation, we show that DHA epoxides, but neither the parent fatty acid nor the corresponding diols, selectively modulate nociceptive pathophysiology. Our findings support an important function of epoxy-fatty acids in the n-3 series in modulating nociceptive signaling. Consequently, the DHA and eicosapentaenoic acid epoxides may be responsible for some of the beneficial effects associated with dietary n-3 fatty acid intake.

Original languageEnglish (US)
Pages (from-to)3481-3490
Number of pages10
JournalJournal of Lipid Research
Volume51
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Central nervous system
  • Pain
  • Soluble epoxide hydrolase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

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