British Journal of Nutrition

Full Papers

Molecular Nutrition

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 Mavrommatisa1, Karen Rossa1, Garry Rucklidgea1, Martin Reida1, Gary Duncana1, Margaret-Jane Gordona1, Frank Thiesa1a2, Alan Sneddona1 and Baukje de Roosa1 c1

a1 Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, UK

a2 Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK

Abstract

Long-chain n-3 PUFA from fish oil protect against death from CHD 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.

(Received November 07 2008)

(Revised June 03 2009)

(Accepted June 04 2009)

(Online publication August 13 2009)

Correspondence:

c1 Corresponding author: Dr Baukje de Roos, fax +44 1224 716629, email b.deroos@abdn.ac.uk

Footnotes

Abbreviations: 2D, two-dimensional; EET, epoxyeicosatrienoic acid; FOXO3a, forkhead box transcription factor 3a; HFC, high-fat high-cholesterol; HOSF, high-oleic acid sunflower-seed; sEH, soluble epoxide hydrolase

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