The role of stable isotopes in the investigation of plasma lipoprotein metabolism.

The last 5 years have seen promising beginnings of the application of stable-isotope-based methods to the study of lipoprotein metabolism. Many aspects of plasma lipid transport make it an attractive system for investigating by this means. While early efforts borrowed from standard techniques of generating and interpreting kinetic parameters (FSRs), the shortcomings of these procedures as applied to lipoproteins are now appreciated. Lipoprotein heterogeneity requires that multicompartmental analysis and relatively long-term studies be employed if the information obtained is going to be a useful adjunct to that produced by radio-iodinated lipoprotein tracers. Both approaches-stable-isotope-labeled endogenous tracer and ex vivo radio-iodinated lipoprotein experiments--must be considered complementary. The first provides direct information on lipoprotein synthesis pathways while the latter is superior at following interconversions and catabolic events. Excellent agreement has been demonstrated where the methods have been used simultaneously to estimate the same kinetic parameter. Many of the questions that have arisen from decades of radioactive tracer studies relate to the nature and rate of lipoprotein synthesis, e.g. what kinds of particles are produced by the liver when different diets are taken, and how are the synthetic pathways altered in dyslipidaemic states? Endogenous tracers can address these issues, and methods are presently available which provide the means for measuring the production of all apolipoproteins and for estimating cholesterol and fatty acid biosynthesis. When techniques are developed to examine triglyceride, cholesteryl ester and phospholipid production then a much clearer picture of how lipoproteins are assembled in vivo will emerge. This kind of information will be essential to an understanding of regulation of plasma lipid transport and the subtle changes that occur in those at risk for coronary heart disease.