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Permanent link (DOI): https://doi.org/10.7939/R3BD37

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The hypolipidemic benefits of trans-11 vaccenic acid in a rat model of dyslipidemia and metabolic syndrome Open Access

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Other title
Subject/Keyword
dyslipidemia
natural trans fat
metabolic syndrome
vaccenic acid
JCR:LA-cp rat
hypertriglyceridemia
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Wang, Ye
Supervisor and department
Proctor, Spencer (Agricultural, Food and Nutritional Science)
Vine, Donna (Agricultural, Food and Nutritional Science)
Examining committee member and department
Proctor, Spencer (Agricultural, Food and Nutritional Science)
Lehner, Richard (Pediatrics)
Field, Catherine (Agricultural, Food and Nutritional Science)
Vine, Donna (Agricultural, Food and Nutritional Science)
Salter, Andrew (Nutritional Sciences, University of Nottingham)
Department
Department of Agricultural, Food and Nutritional Science
Specialization

Date accepted
2010-09-30T16:03:08Z
Graduation date
2010-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Trans-11 vaccenic acid (VA) is the predominant trans fatty acid in dairy fat and is the major precursor to endogenous synthesis of cis9,trans11-conjugated linoleic acid (CLA) in humans and animals. Epidemiological studies have shown the positive association between trans fat intake and incidence of coronary heart disease. Nevertheless, CLA, categorized as a group of trans fatty acids, has been shown to possess anti-carcinogenic, hypolipidemic and anti-diabetic benefits in several animal models as well as certain human populations, possibly via activating peroxisome proliferator-activated receptor (PPAR) related metabolic pathways. The subsequent effort in enriching CLA in dairy products (e.g. butter) has led to a concomitant increase in VA, whose bioactivity and health implications were not fully appreciated. Interestingly, VA is the major natural trans fat found in the diet. Therefore, the objectives of this thesis were to assess the effect of dietary supplementation of synthetic VA on lipid metabolism especially during conditions of dyslipidemia and metabolic syndrome, and to delineate the intestinal and hepatic metabolic pathways potentially modulated by VA. The JCR:LA-cp rat model, when homozygous for the cp trait (cp/cp), develop leptin receptor deficiency which leads to symptoms of metabolic syndrome and pre-diabetes including obesity, insulin resistance, hepatic steatosis, hypertriglyceridemia and exacerbated production of hepatic very low-density lipoproteins and intestinal chylomicrons (CM). Gas chromatography analysis on nascent lymph shows that VA was effectively absorbed into the intestine. In addition, VA from natural source (i.e. beef fat) showed higher intestinal bioavailability compared to synthetic VA. Dietary supplementation of 1.0% (w/w) synthetic VA to JCR:LA-cp rats (but not lean healthy controls) demonstrated a profound reduction in plasma triglyceride, total cholesterol, low-density lipoprotein-cholesterol, non-esterified fatty acid and haptoglobin concentrations (51%, p<0.001; 40%, p<0.001; 50%, p<0.05; 20%, p<0.05 and 50%, p<0.001; respectively), as well as improvement in hepatic steatosis and postprandial lipaemia. Gastric infusion of VA also resulted in an acute reduction in CM secretion in response to a fat load (p<0.05). We also found that the overall hypolipidemic benefits of VA might be partially contributed by suppression of hepatic de novo lipogenesis, activation of PPAR-α activity as well as up-regulation of PPAR-α and PPAR-γ expression in the intestine. In conclusion, VA as a natural trans fat, possesses beneficial properties in a rat model of dyslipidemia and metabolic syndrome, suggesting potential for the prevention of cardiovascular disease risk.
Language
English
DOI
doi:10.7939/R3BD37
Rights
License granted by Ye Wang (ye3@ualberta.ca) on 2010-09-29T20:02:19Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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