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No description available.

Intestinally derived chylomicron remnants (CM-r) may contribute to atherogenic dyslipidemia during the Metabolic Syndrome (Mets). However, the combined effects of ezetimibe (EZ) and simvastatin (SV) on post-prandial (PP) dyslipidemia during MetS remains unclear, nor is it known whether the combination has a synergistic anti-atherogenic effect on CM-r arterial retention. The first objective was to delineate the effects of EZ+SV therapy on intestinal cholesterol flux and CM PP metabolism in the JCR:LA-cp rat, a model of MetS. The second objective was to quantify the impact of EZ+SV therapy on arterial retention of CM-r and subsequent myocardial lesion development in the JCR:LA-cp rat. EZ+SV therapy decreased net intestinal cholesterol absorption in MetS rats. Furthermore, EZ+SV therapy reduced arterial retention of CM-r and frequency of myocardial lesions in MetS rats. In conclusion, EZ+SV therapy reduces arterial retention of CM-r and myocardial lesion development possibly through its beneficial effects on cholesterol transport and PP-metabolism. / Nutrition and Metabolism

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- activity as well as up-regulation of PPAR- and PPAR- 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. / Nutrition and Metabolism