Plasma clearance and tissue distribution of liposomes containing different sterols.

was precipitated (Kane et al., 1975) with 1,1,3,3-tetramethylurea, extracted with chloroform/methanol (1 : 1, v/v), washed with ether, and dried under N2. Amino acid analysis of this protein corresponded to that of apolipoprotein B, as did its electrophoretic mobility on urea/polyacrylamide-gel electrophoresis. Its specific radioactivity was obtained by radioactivity counting and protein determination (Lowry et al., 1951), after dissolving in 1.0ml of O . ~ M N ~ O H . On both diets the protein was cleared from the plasma following first-order kinetics. The slope of the decay curve was therefore a measure of the fractional clearance rate of apolipoprotein B. This value, together with the VLD-apolipoprotein obtained from a known volume of plasma), was used to calculate the synthetic rate of the protein (the product of the fractional clearance rate and pool size in the steady state). With respect to diet S, diet P produced a consistent fall in the total plasma concentration of cholesterol, triacylglycerol and VLD apolipoprotein B (Table l), with significant alteration of the composition of this lipoprotein. The most prominent diet-induced compositional changes were seen in the palmitate, oleate and linoleate content of VLD cholesteryl esters, triacylglycerols and phospholipids. In general the percentages of palmitate and oleate fell in these moieties, whereas that of linoleate increased. These alterations in VLD-lipoprotein fatty acyl content were accompanied by modification of the gross composition of the lipoprotein, resulting in particles of increased triacylglycerol content and decreased in phospholipid. The kinetic parameters of VLD-apolipoprotein-B decay (Table 1) indicated that the fall in plasma VLD-apolipoprotein-B concentration on diet P resulted not from an increase in the fractional clearance rate of the protein but rather from a 36%(P<0.01) decrease in its rate of synthesis. From these data we conclude that the rate of synthesis of VLD apolipoprotein B in normal subjects on a polyunsaturated-fat diet is decreased, and this is accompanied by a significant change in the composition of the circulating lipoprotein.