title: Intervention with fish oil, but not with docosahexaenoic acid, results in lower levels of hepatic soluble epoxide hydrolase with time in apoE knockout mice.
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.
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Mavrommatis
authors.forename: Karen
authors.initials: K
authors.lastname: Ross
authors.forename: Garry
authors.initials: G
authors.lastname: Rucklidge
authors.forename: Martin
authors.initials: M
authors.lastname: Reid
authors.forename: Gary
authors.initials: G
authors.lastname: Duncan
authors.forename: Margaret-Jane
authors.initials: MJ
authors.lastname: Gordon
authors.forename: Frank
authors.initials: F
authors.lastname: Thies
authors.forename: Alan
authors.initials: A
authors.lastname: Sneddon
authors.forename: Baukje
authors.initials: B
authors.lastname: de Roos
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000473:pathology* / Q000517:prevention & control; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D017931:DNA Primers; D004041:Dietary Fats; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism*; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019301:Oleic Acid / Q000494:pharmacology*; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012639:Seeds; D013045:Species Specificity
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D017931:DNA Primers; D004041:Dietary Fats; D005395:Fish Oils; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D004851:Epoxide Hydrolases