Regulation of triclyceride-rich lipoprotein metabolism in obesity: impact of w-3 fatty acid ethyl ester supplementation

Annette Tsz Yan Wong

    Research output: ThesisDoctoral Thesis

    151 Downloads (Pure)

    Abstract

    [Truncated] Hypertriglyceridaemia, due to increased plasma concentrations of hepatic apolipoprotein (apo) B-100 and intestinal apoB-48, is the most consistent lipid disorder in visceral obesity and is a risk factor for cardiovascular disease. The precise mechanisms whereby obesity results in hypertriglyceridaemia have not been fully established, but may involve alterations in the kinetics of triglyceride-rich chylomicrons and very-low-density lipoproteins (VLDL).
    This thesis tests the principal hypothesis that obese individuals have impaired triglyceride-rich lipoprotein (TRL) metabolism, and that supplementation with ω-3 fatty-acid ethyl esters (ω-3 FAEE) will improve TRL metabolism, and by implication lower cardiovascular risk. The aims of this thesis were to test the subhypotheses and observational statements derived from the principal hypothesis. These were tested in four corresponding studies. The inferences made in this thesis were based on both deductive and inductive reasoning.
    VLDL-triglyceride and apoB-48 kinetics were measured after a bolus injection of d5-glycerol and d3-leucine, respectively. Isotopic enrichments of VLDL-triglyceride and apoB-48 were determined using gas chromatography mass spectrometry (GCMS) and kinetic parameters were derived using multi-compartmental models (Simulation, Analysis, and Modelling Software II, or SAAMII).
    The studies employed to test the general hypothesis were based on two controlled clinical trials to examine the effect of ω-3 FAEE on VLDL-triglyceride and chylomicron (CM) apoB-48 in obese subjects with dyslipidaemia. The findings (Studies 14) are presented separately as a series of original publications.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2014

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