Fish oils, phytosterols and weight loss in the regulation of lipoprotein transport in the metabolic syndrome: lessons from stable isotope tracer studies.

1. Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is characterized by high plasma concentrations of triglyceride-rich and apolipoprotein (apo) B-containing lipoproteins, with depressed concentrations of high-density lipoprotein (HDL). Dysregulation of lipoprotein metabolism in these subjects may be due to a combination of overproduction of very-low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles and increased catabolism of HDL apoA-I particles. 2. Nutritional interventions may favourably alter lipoprotein transport in the metabolic syndrome. We review our collaborative studies, using stable isotopes and compartmental modelling, of the kinetic effects of fish oils, plant sterols (phytosterols) and weight reduction on the dyslipoproteinaemia in this disorder. 3. Fish oil supplementation diminished hepatic secretion of VLDL-apoB and enhanced conversion of VLDL to low-density lipoprotein (LDL)-apoB, without altering catabolism. 4. Plant sterols (phytosterols) did not have a significant effect on plasma concentrations of lipids and lipoprotein or the kinetics of apoB and apoA-I. 5. Modest weight reduction optimally decreased plasma triglyceride and LDL-cholesterol via reduction in hepatic apoB secretion and reciprocal upregulation of LDL catabolism. 6. The scope and potential of future studies using stable isotope tracers is discussed.