Influence of lipolysis on chylomicron clearance and HDL cholesterol levels

Atherogenic risk is accurately defined by the turnover of the lipoprotein classes that transport cholesterol and triglycerides, and by the apolipoproteins that determine the fate of these particles. Post-prandial triglyceride levels have also been shown to be an accurate predictor of atherogenic risk. The post-prandial triglyceride levels and conversion of very low density lipoprotein (VLDL) to intermediate density lipoprotein (IDL) are controlled by a dynamic metabolic process involving lipoprotein lipase (LPL) and hepatic lipase. The interaction between the two enzymes modulates triglyceride transport through the plasma and influences the structure and serum concentrations of the denser cholesterol-rich low density lipoproteins (LDL) and high density lipoproteins (HDL). Inadequate LPL function, a consequence either of impaired enzyme function or simply post-prandial overloading, can have profound pathophysiological consequences. High levels of large HDL2 reflect effective catabolism of triglyceride-rich lipoproteins by LPL whereas low levels of this lipoprotein reflect inadequate LPL activity or elevated hepatic lipase activity. Individuals with low levels of HDL2 are prone to coronary artery disease. Overloading of LPL can occur in insulin resistance due to the absence of normal insulin-mediated suppression of VLDL secretion and the consequence is hypertriglyceridaemia. In addition, a deficiency in LPL can arise from a genetic defect which, in the homozygous state, results in pronounced hypertriglyceridaemia and pancreatitis. The correct management for patients with inadequate LPL activity is to optimize triglyceride metabolism, particularly in the post-prandial state.