Dyslipoproteinaemia is a cardinal feature of the
metabolic syndrome that accelerates
atherosclerosis. It is usually characterised 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. These abnormalities may be consequent on a global metabolic effect of
insulin resistance that increases the flux of
fatty acids from adipose tissue to the liver, the accumulation of fat in the liver, the increased hepatic secretion of VLDL-
triglycerides and the remodelling of both
low-density lipoprotein (
LDL) and HDL particles in the circulation; perturbations in lipolytic
enzymes and
lipid transfer
proteins contribute to the dyslipidaemia. Our in vivo understanding of the kinetic defects in
lipoprotein metabolism in the
metabolic syndrome has been chiefly achieved by ongoing developments in the use of stable
isotope tracers and mathematical modelling. Knowledge of the pathophysiology of
lipoprotein metabolism in the
metabolic syndrome is well complemented by extensive cell
biological data. Nutritional modifications and increased physical exercise may favourably alter
lipoprotein transport in the
metabolic syndrome by collectively decreasing the hepatic secretion of VLDL-
apoB and the catabolism of HDL
apoA-I, as well as by increasing the clearance of
LDL-
apoB. Pharmacological treatments, such as
statins,
fibrates or
fish oils, can also correct the dyslipidaemia by several mechanisms of action including decreased secretion and increased catabolism of
apoB, as well as increased secretion and decreased catabolism of
apoA-I. The complementary mechanisms of action of lifestyle and
drug therapies support the use of combination regimens to treat dyslipidaemia in the
metabolic syndrome.