Abstract
To estimate hepatic uptake of chylomicron remnants in humans, chylomicrons and intestinal very low density lipoproteins (VLDL) were endogenously labeled with retinyl esters, harvested by plasmapheresis, and pulse-injected into the donor 44 hr after plasmapheresis. Plasma decay of retinyl palmitate was measured in eight healthy volunteers. Retinyl palmitate plasma disappearance obeyed an apparent first order function in seven studies and, in one study, a biexponential function with the second, slow exponential accounting for only 13% of the retinyl palmitate plasma decay. The mean fractional removal of rate was 0.037 +/- 0.037 min-1 (mean +/- SD) in a one-compartment model. The apparent volume of distribution, Vd, was 109 +/- 25% of the estimated plasma volume. Plasma clearance of retinyl palmitate was 130 +/- 97 ml/min calculated as Vd x Ke. Mean T 1/2 was 29 +/- 16 min. Both in vitro and in vivo the retinyl palmitate remained largely within chylomicrons and intestinal VLDL. Only 4.3% was transferred from chylomicrons to other lipoprotein classes during in vitro incubation for 5 hr. After plasma was stored for 42 hr, 5% was transferred to higher density lipoproteins. During 12 hr after a test meal containing retinyl palmitate, only 6.4 +/- 1.5% of the retinyl palmitate absorbed was found in the LDL fraction and 3.1 +/- 3.8% in the d 1.063 g/ml lipoproteins. We conclude that retinyl palmitate is a useful marker for chylomicrons and their remnants in humans and that the plasma clearance of retinyl palmitate-labeled chylomicrons is probably an estimate of chylomicron remnant plasma clearance in man.
Highlights
Chylomicron remnants cannot be selectively isolated in seven studiesand, in one study,a biexponential functionwith the second, slow exponential accounting for only 13% of the retinyl palmitate plasma decay
T h e inhibition of cholesterol synthesis accompanying expansion ofthe bile acid pool in rats is mediated through increased intestinal cholesterol absorption and increased hepatic chylomicron remnantuptake [3]
We investigated the followingspecificquestionsin healthyhumansubjects: 1. T o what extent are retinyl esterstransferred from chylomicronsand intestinal very low density lipoproteins (VLDL) to low density lipoproteins(d 1.019-1.063 g/ml) (LDL) and high density lipoproteins (HDL) in vitro and in vivo? 2.What are the kinetic characteristicosf plasmaclearanceof intravenously administered chylomicronslabeledwithretinylpalmitate (RP)?
Summary
Chylomicron remnants cannot be selectively isolated in seven studiesand, in one study,a biexponential functionwith the second, slow exponential accounting for only 13% of the retinyl palmitate plasma decay. Since esterified cholesterol in the core of chylomicrons and VLDL is exchanged with the cholesterol in other lipoprotein classes during its circulation in the k 25% of the estimatedplasmavolume.Plasmaclearance of plasma, mediated by cholesteryl ester exchange protein retinyl palmitate was 130 f 97 ml/min calculated as Vd X K,. Mahley, and Buckhold [9] used retinyl esters to Supplementarykey wordn retinyl palmitate transfer retinyl palmitate study plasma clearance of chylomicron remnantsin dogs distribution and found some transfer of esters to higher density lipoproteinfractions, due either to cholesteryl ester exchange protein or possibly to resecretion by the liver. Hepatic cholesterol synthesis in the ratis regulated, in The extentof such a transfer of retinyl esters,if any, in part, by the size of the bile acid pool in the enterohepatic man is not known. Validated methods for measurement ofbile acid pool size [4] and cholesterol absorption ( 5 ) are available, buthepatic chylomicron (1,*2T).o whom reprint requests should be Sent at: Division of Gastroenterology, B-158 University of Colorado School of Medicine 4200
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