Plasma decay of chylomicron remnants is not affected by heparin-stimulated plasma lipolytic activity in normal fasting man1

In an earlier study it was shown that retinyl palmitate appeared to be a satisfactory label for the core of chylomicrons and their remnants. When chylomicrons were endogenously labeled with retinyl palmitate and pulse-injected into healthy donors, retinyl palmitate was cleared from plasma by a first order process. Its fractional decay constant was very similar to the fractional catabolic rate of VLDL triglycerides, a lipoprotein lipase-dependent process, and 2-3 times slower than hepatic chylomicron remnant uptake in experimental animals. We, therefore, investigated whether plasma clearance of retinyl palmitate-labeled chylomicrons is accelerated by enhanced plasma triglyceride hydrolysis produced by heparin administration. Five healthy subjects took retinyl palmitate by mouth and 5-6 hr later two units of plasma were obtained by plasmapheresis. After storage for 42 hr, the units were pooled and separated into two equal volumes. The first half was injected into the donor and plasma retinyl palmitate and chylomicron triglyceride were measured for 3.5 hr (control study). Heparin was then given intravenously as a bolus followed by an infusion for 7 hr. A second retinyl palmitate clearance (postheparin study) was performed during the heparin infusion. Plasma lipolytic activity and retinyl palmitate and chylomicron triglyceride concentrations were measured serially. Total plasma lipolytic activity and hepatic triglyceride lipase activity were increased approximately 500-fold during postheparin studies, enhancing triglyceride decay 2.5to 3-fold. Retinyl plamitate plasma decay, however, was unaffected. Retinyl palmitate plasma decay was a biexponential concentration-dependent function in eight of ten preand postheparin studies with the first, rapid exponential accounting for 90 5 4% of total plasma retinyl palmitate decay. There were no significant differences in clearance rates of total plasma retinyl palmitate (100 * 27 vs 108 f 27 ml/min) or in the rapid or slow decay constants. The apparent volume of distribution of retinyl palmitate in relation to estimated plasma volume was comparable in control and postheparin studies (99 f 11% vs 109 f 22%). Although heparin accelerates chylomicron triglyceride hydrolysis and remnant formation, it does not affect plasma clearance of chylomicron remnants labeled with retinyl palmitate. We conclude that these findings are strong evidence that chylomicron remnant clearance is not limited by the rate of chylomicron remnant formation in normal fasting man. The plasma clearance rate of retinyl palmitatelabeled chylomicrons is an estimate of chylomicron remnant clearance. -Ben, F., R. Eckel, and F. Kern, Jr. Plasma decay of chylomicron remnants is not affected by heparin-stimulated plasma lipolytic activity in normal fasting man. J. Lipid Res. 1985. 26: 852-859. Supplementary key words retinyl palmitate postheparin lipoprotein lipase heparin-enhanced triglyceride lipolysis The plasma clearance of chylomicron remnants by the liver has not been quantitated in man. Labeling techniques for either core constituents or the remnant lipoproteins have not been satisfactory. Recently we evaluated a method for measuring chylomicron clearance using retinyl palmitate (RP) to label the core of chylomicrons and intestinal VLDL (3). Most RP remains in the lipid core of chylomicrons and their remnants until the remnants are cleared by the liver, and only 5 to 10% is transferred to other lipoproteins (3-6). When RP-labeled chylomicrons are administered intravenously in RP-enriched autologous plasma, they distribute in the plasma volume and are cleared by a concentration-dependent process, probably reflecting hepatic chylomicron remnant uptake (3). The removal rate, however, is 2-3 times slower than reported for chylomicron remnants in animals (7-9) and similar to the plasma triglyceride turnover in man, a process mediated by lipoprotein lipase (10, 11). To determine whether chylomicron triglyceride hydrolysis is the rate-limiting step in plasma clearance of RPlabeled chylomicron remnants, we measured plasma Abbreviations: HDL, high density lipoproteins (d 1.063-1.21 g/ml); LDL, low density lipoproteins (d 1.019-1.063 g/ml); VLDL, very low density lipoproteins (d < 1.006 g/ml); HPLC, high performance liquid chromatography; V,, apparent volume of distribution; k,, apparent fraction elimination constant; RP, retinyl palmitate. 'Preliminary reports have appeared in abstract form (1, 2). 'To whom reprint requests should be addressed at: GI-Division B-158, University of Colorado School of Medicine, 4200 East Ninth Avenue, Denver, CO 80262. 852 Journal of Lipid Research Volume 26, 1985 by gest, on O cber 8, 2017 w w w .j.org D ow nladed fom decay of R P before and during triglyceride lipolysis enhanced by heparin in five healthy subjects. We used continuous intravenous heparin infusion, which accelerates chylomicron triglyceride removal 2to %fold by release of lipoprotein lipase (12).