Controlled dietary studies will be carried out in 40 Caucasian males to determine the effects of dietary cholesterol on the apolipoprotein and lipid composition of plasma lipoprotein subfractions and the plasma phosphatidylcholine/free cholesterol ratio and to define the metabolic and genetic basis of these effects. A random crossover design will be used such that each subject will ingest two solid food diets identical in macro- and micronutrient composition and differing in cholesterol content (150 vs 950 mg/d). The metabolic responses to dietary cholesterol including cholesterol absorption, cholesterol synthesis, and low density lipoprotein B kinetic parameters will be investigated in subjects differing in apolipoprotein E phenotype. The relationship between a specific restriction fragment length polymorphism adjacent to the apolipoprotein AII gene and the metabolic responses to dietary cholesterol will also be determined. Studies will be performed in the postprandial state in individuals defined in terms of 1) apolipoprotein E phenotype, 2) a specific restriction fragment length polymrphism adjacent to apolipoprotein AII, 3) hepatic lipase activity and 4) metabolic responsiveness to dietary cholesterol. Retinyl palmitate labelled chylomicrons will be used to determine chylomicron remnant kinetics and attendant changes in the composition of plasma lipoprotein subfractions following consumption of a lipid emulsion (35 g corn oil) with and without 600 mg of solubilized cholesterol. These experiments will investigate the hypothesis that factors regulating chylomicron remnant clearance by the liver such as apolipoprotein E pheno type and hepatic lipase activity, will affect the plasma low density lipoprotein cholesterol response to dietary cholesterol such that more effective hepatic clearance of chylomicron remnants results in increased hepatic cholesterol, down-regulation of the hepatic B/E receptor and impaired low density lipoprotein clearance.
|Kisucka, Janka; Butterfield, Catherine E; Duda, Dan G et al. (2006) Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage. Proc Natl Acad Sci U S A 103:855-60|
|McPherson, R; Marcel, Y (1991) Role of cholesteryl ester transfer protein in reverse cholesterol transport. Clin Cardiol 14:I31-4|
|McPherson, R; Mann, C J; Tall, A R et al. (1991) Plasma concentrations of cholesteryl ester transfer protein in hyperlipoproteinemia. Relation to cholesteryl ester transfer protein activity and other lipoprotein variables. Arterioscler Thromb 11:797-804|
|McPherson, R; Hogue, M; Milne, R W et al. (1991) Increase in plasma cholesteryl ester transfer protein during probucol treatment. Relation to changes in high density lipoprotein composition. Arterioscler Thromb 11:476-81|