title: Chronic dietary n-3 PUFA intervention improves dyslipidaemia and subsequent cardiovascular complications in the JCR:LA- cp rat model of the metabolic syndrome.
abstract: There is increasing interest in the potential chronic beneficial effects of dietary n-3 PUFA on the metabolic syndrome (MetS) and associated cardiovascular complications. We have recently established that increased dietary n-3 PUFA has a profound acute benefit on fasting lipids and the postprandial pro-inflammatory response in the JCR:LA-cp rat, a model of the MetS. However, it is unclear to what extent chronic dietary n-3 PUFA intervention can modulate the progression of end-stage metabolic and vascular complications. The present study aimed to determine the chronic effects of dietary n-3 PUFA supplementation on fasting and non-fasting dyslipidaemia, insulin resistance and vascular complications in the JCR:LA-cp rodent model. JCR:LA-cp rats were fed an isoenergetic lipid-balanced diet supplemented with 5 % n-3 PUFA (w/w) of the total fat (fish oil-derived EPA/DHA) for 16 weeks. Fasting and non-fasting (postprandial) plasma lipid profile was assessed. Hepatic and adipose tissue was probed for the expression of lipogenic proteins (acyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element-binding protein-1 (SREBP-1)), while the activity of Jun N-terminal kinase (JNK) was assessed via Western blot to target phosphorylated JNK protein in primary enterocytes. The frequency of myocardial lesions was assessed by haematoxylin and eosin staining. Increased dietary n-3 PUFA improved both the fasting and postprandial lipid profiles (TAG, cholesterol and apoB48) in the JCR:LA-cp rat, potentially via the down-regulation of the hepatic or adipose tissue expression of lipogenic enzymes (ACC, FAS and SREBP-1). Rats fed the 5 % n-3 PUFA diet had lower (58·2 %; P < 0·01) enterocytic phosphorylated JNK protein and secreted less cholesterol (30 %; P < 0·05) into mesenteric lymph compared with the control. The chronic metabolic benefits of dietary n-3 PUFA may underlie the potential to reduce vascular complications during the MetS, including the observed reduction in the frequency (approximately 80 %) of late-stage 3 myocardial lesions.
authors.affiliation: Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, 4-10 Agriculture Forestry Centre, University of Alberta, Edmonton, AB, Canada T6G 2P5.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Faye
authors.initials: F
authors.lastname: Borthwick
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hassanali
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Rabban
authors.initials: R
authors.lastname: Mangat
authors.forename: Megan
authors.initials: M
authors.lastname: Ruth
authors.forename: Danni
authors.initials: D
authors.lastname: Shi
authors.forename: Anja
authors.initials: A
authors.lastname: Jaeschke
authors.forename: James C
authors.initials: JC
authors.lastname: Russell
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Field
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Proctor
authors.forename: Donna F
authors.initials: DF
authors.lastname: Vine
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004032:Diet; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D050171:Dyslipidemias / Q000097:blood / Q000178:diet therapy*; D004435:Eating / Q000187:drug effects; D020895:Enterocytes / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007583:Jejunum / Q000166:cytology; D008055:Lipids / Q000097:blood; D008196:Lymph / Q000737:chemistry; D008297:Male; D024821:Metabolic Syndrome / Q000178:diet therapy*; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000235:genetics; D019518:Postprandial Period; D011897:Random Allocation; D051381:Rats
chemical_list: D015525:Fatty Acids, Omega-3; D008055:Lipids