Recent advances in the investigation of lipoprotein metabolism using tracer methodology

Dyslipidemia, the most consistent lipid disorder in subjects with obesity and type 2 diabetes mellitus, is associated with increased risk of coronary artery disease. Lipoprotein metabolism is complex and abnormal plasma concentrations can result from alterations in the rates of production and/or catabolism of the various lipoprotein particles. Our in vivo understanding of kinetic defects in lipoprotein metabolism in these subjects has relied on ongoing developments in the use of stable isotope tracers and mathematical modelling. This review deals with the methodological and clinical 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, laboratory isolation and measurement of tracer, and interpretation of tracer data, all of which are critically dependent on the kinetic properties of the lipoproteins under investigation. Such stable isotope tracer techniques have provided a mechanistic insight into the understanding of lipoprotein disorders and effects of treatments in the metabolic syndrome. Further development in tracer methodologies, with practicable in-vivo protocols, are required for investigating cholesterol transport in plasma, tissue lipid metabolism, such as cholesterol and lipid transport in macrophages, liver and skeletal muscle, and the turnover of subpopulations of HDL particles involved in reverse cholelsterol transport.