title: Hypercholesterolaemia alters the responses of the plasma lipid profile and inflammatory markers to supplementation of the diet with n-3 polyunsaturated fatty acids from fish oil.
abstract: BACKGROUND
  The influence of supplementing the diet with long-chain n-3 polyunsaturated fatty acids (PUFA) from fish oil on plasma lipids and lipid peroxides and the production of pro-inflammatory mediators in normolipidaemic and hypercholesterolaemic rats were studied.
  
  
  METHODS
  Rats were divided into four groups and fed one of the following diets: a control diet (containing 4% corn oil); an n-3 PUFA diet [containing 4% eicospentaenoic (EPA) + docosahexaenoic (DHA)]; a hypercholesterolaemic diet (HCH); or a HCH + n-3 PUFA diet over a 4-week period. Plasma lipids, lipid peroxides, cytokines [tumour necrosis factor (TNF)alpha, interleukin (IL)-6, interferon (IFN)gamma] and mRNA for hepatic nuclear factor-4alpha (HNF4alpha) were determined.
  
  
  RESULTS
  Plasma triglyceride (TG), but not cholesterol, levels were decreased by the n-3 PUFA as compared with the control diet (P < 0.001), but the addition of n-3 PUFA to the HCH diet decreased both the TG (P < 0.01) and cholesterol (P < 0.05) concentrations. Plasma lipid peroxides and expression HNF4alpha mRNA were increased by n-3 PUFA in the normolipidaemic (P < 0.05), but not in the hyperlipidaemic rats. Compared with the control diet group, plasma concentrations of TNFalpha and IL-6 were increased in the n-3 PUFA (P < 0.05) and HCH diet (P < 0.05, P < 0.01, respectively) groups, but not in animals given the HCH + n-3 PUFA diet, whereas IFNgamma levels were increased in hypercholesterolaemia (P < 0.05), but were unaffected by n-3 PUFA.
  
  
  CONCLUSIONS
  These results demonstrate that the major effect of fish oil n-3 PUFA is to lower the TG levels in both normo- and hyperlipidaemia. Furthermore, in the hypercholesterolaemic state, fish oil n-3 PUFA induces additional beneficial changes in the immune and peroxidation responses.
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy. bravo@iss.it
authors.forename: E
authors.initials: E
authors.lastname: Bravo
authors.forename: M
authors.initials: M
authors.lastname: Napolitano
authors.forename: I
authors.initials: I
authors.lastname: Lopez-Soldado
authors.forename: M
authors.initials: M
authors.lastname: Valeri
authors.forename: K M
authors.initials: KM
authors.lastname: Botham
authors.forename: C
authors.initials: C
authors.lastname: Stefanutti
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004042:Dietary Fats, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology*; D005395:Fish Oils / Q000008:administration & dosage; D051557:Hepatocyte Nuclear Factor 4; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology*; D008054:Lipid Peroxides / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D012333:RNA, Messenger / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D051557:Hepatocyte Nuclear Factor 4; D008054:Lipid Peroxides; D008055:Lipids; D012333:RNA, Messenger