METABOLIC BASIS FOR HYPERTRIGLYCERIDEMIA IN FAMILIAL COMBINED HYPERLIPIDEMIA

Familial combined hyperlipidaemia (FCH) is not a single entity with a clearly defined cause but can occur through an increased fatty acid fl ux from adipose cells, lipoprotein lipase dysfunction or apolipoprotei n CIII abnormalities. A dynamic model of the metabolic processes of FC H has been used to describe how lipolysis of adipose cells may ultimat ely contribute to the formation of atherosclerotic plaques. Elevated c irculating levels of chylomicrons are broken down to produce atherogen ic remnants. One of the roles of lipoprotein lipase is in the low dens ity lipoprotein (LDL) receptor-like protein-mediated uptake of lipopro tein remnants in the liver and up to 20% of FCH patients show a geneti c abnormality of this enzyme. Vitamin A loading and measurement of chy lomicron retinyl palmitate levels has further demonstrated impaired ch ylomicron remnant metabolism in these patients. Macrophages located in the vascular walls engulf remnants but are unable to metabolize their cholesterol. These cells contribute to atherosclerotic plaques. In te rms of atherogenic potential, triglyceride levels are found to be high er and the hypertriglyceridaemia more severe in fed than in fasted pat ients. A case study of a patient with abetalipoproteinaemia suggests t hat the hypertriglyceridaemia seen in patients with FCH may be the res ult of an abnormality in microsomal triglyceride transport protein fun ction. Studies also suggest a direct relationship between the post-pra ndial triglyceride levels and LDL cholesterol levels in the fasting st ate of patients with FCH and sporadic hypercholesterolaemia.