Lipoprotein transport in the metabolic syndrome: methodological aspects of stable isotope kinetic studies.
The metabolic syndrome encapsulates visceral obesity, insulin resistance, diabetes, hypertension and dyslipidaemia. Dyslipidaemia is a cardinal feature of the metabolic syndrome that accelerates the risk of cardiovascular disease. It is usually characterized by high plasma concentrations of triacylglycerol (triglyceride)-rich and apoB (apolipoprotein B)-containing lipoproteins, with depressed concentrations of HDL (high-density lipoprotein). However, lipoprotein metabolism is complex and abnormal plasma concentrations can result from alterations in the rates of production and/or catabolism of these lipoprotein particles. Our in vivo understanding of kinetic defects in lipoprotein metabolism in the metabolic syndrome has been achieved chiefly by ongoing developments in the use of stable isotope tracers and mathematical modelling. This review deals with the methodological aspects of stable isotope kinetic studies. The design of in vivo turnover studies requires considerations related to stable isotope tracer administration, duration of sampling protocol and interpretation of tracer data, all of which are critically dependent on the kinetic properties of the lipoproteins under investigation. Such models provide novel insight that further understanding of metabolic disorders and effects of treatments. Future investigations of the pathophysiology and therapy of the dyslipoproteinaemia of the metabolic syndrome will require the development of novel kinetic methodologies. Specifically, new stable isotope techniques are required for investigating in vivo the turnover of the HDL subpopulation of particles, as well as the cellular efflux of cholesterol into the extracellular space and its subsequent transport in plasma and metabolic fate in the liver.
Chan
Dick C
DC
Lipoprotein Research Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6847.
Barrett
P Hugh R
PH
Watts
Gerald F
GF
D001692:Biological Transport; D003627:Data Interpretation, Statistical; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D007554:Isotopes / Q000493:pharmacokinetics; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000097:blood*
D007554:Isotopes; D008074:Lipoproteins