Metabolic basis for hypertriglyceridaemia in familial combined hyperlipidaemia.
Familial combined hyperlipidaemia (FCH) is not a single entity with a clearly defined cause but can occur through an increased fatty acid flux from adipose cells, lipoprotein lipase dysfunction or apolipoprotein CIII abnormalities. A dynamic model of the metabolic processes of FCH has been used to describe how lipolysis of adipose cells may ultimately contribute to the formation of atherosclerotic plaques. Elevated circulating levels of chylomicrons are broken down to produce atherogenic remnants. One of the roles of lipoprotein lipase is in the low density lipoprotein (LDL) receptor-like protein-mediated uptake of lipoprotein remnants in the liver and up to 20% of FCH patients show a genetic abnormality of this enzyme. Vitamin A loading and measurement of chylomicron retinyl palmitate levels has further demonstrated impaired chylomicron 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 terms of atherogenic potential, triglyceride levels are found to be higher and the hypertriglyceridaemia more severe in fed than in fasted patients. A case study of a patient with abetalipoproteinaemia suggests that the hypertriglyceridaemia seen in patients with FCH may be the result of an abnormality in microsomal triglyceride transport protein function. Studies also suggest a direct relationship between the post-prandial triglyceride levels and LDL cholesterol levels in the fasting state of patients with FCH and sporadic hypercholesterolaemia.
Erkelens
D W
DW
Academisch Ziekenhuis Utrecht, The Netherlands.
D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000235:genetics*; D006953:Hyperlipoproteinemia Type IV / Q000097:blood / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics; D008066:Lipolysis / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
D014280:Triglycerides