Chronic dietaryn-3 PUFA intervention improves dyslipidaemia and subsequent cardiovascular complications in the JCR:LA-cprat model of the metabolic syndrome

Abstract

There is increasing interest in the potential chronic beneficial effects of dietaryn-3 PUFA on the metabolic syndrome (MetS) and associated cardiovascular complications. We have recently established that increased dietaryn-3 PUFA has a profound acute benefit on fasting lipids and the postprandial pro-inflammatory response in the JCR:LA-cprat, a model of the MetS. However, it is unclear to what extent chronic dietaryn-3 PUFA intervention can modulate the progression of end-stage metabolic and vascular complications. The present study aimed to determine the chronic effects of dietaryn-3 PUFA supplementation on fasting and non-fasting dyslipidaemia, insulin resistance and vascular complications in the JCR:LA-cprodent model. JCR:LA-cprats 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 dietaryn-3 PUFA improved both the fasting and postprandial lipid profiles (TAG, cholesterol and apoB48) in the JCR:LA-cprat, 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 dietaryn-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.