Intervention with fish oil, but not with docosahexaenoic acid, results in lower levels of hepatic soluble epoxide hydrolase with time in apoE knockout mice

Yiannis Mavrommatis, Karen Ross, Garry Rucklidge, Martin Reid, Gary James Duncan, Margaret Jane Gordon, Frank Thies, Alan Arthur Sneddon, Baukje De Roos

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Long-chain n-3 PUFA from fish oil protect against death from CHID but mechanisms are not well understood. Preliminary results indicate that fish oil may affect the enzyme soluble epoxide hydrolase (sEH) and influence inflammatory pathways in a time-dependent manner. In the present study male apoE knockout (Apoe(-/-)) mice were randomised to three dietary groups receiving a high-fat high-cholesterol diet supplemented with 2% (w/w) high-oleic acid sunflower-seed (HOSF) oil, DHA oil or fish oil. Livers and proximal aortas were collected on day 2 and on weeks 1, 2, 4 and 10 to determine hepatic sEH levels, hepatic fatty acid composition, hepatic proteome and atherosclerotic plaque size in the aortic root. Intervention with fish oil, but not with DHA, resulted in significantly lower levels of hepatic sEH levels with time compared with HOSF oil. DHA and fish oil caused differential regulation of thirty-five hepatic proteins which were mainly involved in lipoprotein metabolism and oxidative stress. All mice developed atherosclerosis without differences in plaque size between the three groups. Thus EPA may be responsible for lowering levels of hepatic sEH and both fish oil and DHA could beneficially affect lipoprotein metabolism and oxidative stress.

Original languageEnglish
Pages (from-to)16-24
Number of pages9
JournalBritish Journal of Nutrition
Issue number1
Early online date13 Aug 2009
Publication statusPublished - 14 Jan 2010


  • epoxyeicosatrienoic acids
  • n-3 Fatty acids
  • proteomics
  • atherosclerosis
  • polyunsaturated fatty-acids
  • coronary heart-disease
  • eicosapentaenoic acid
  • atherosclerotic lesions
  • dietary supplementation
  • myocardial-infarction
  • APOE(-/-) MICE
  • metabolism
  • liver
  • Epoxyeicosatrienoic acids
  • Proteomics
  • Atherosclerosis

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