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Hepatic uptake of phospholipid-depleted chylomicrons in vivo. Comparison with the uptake of chylomicron remnants.

ABSTRACT: 1. Rats pretreated with Triton WR-1339 to prevent the formation of remnants were injected with [3H]cholesterol-labelled remnants, intact chylomicrons or chylomicrons depleted of most of their surface phospholipids by treatment with phospholipase A2. Within 5 min about 80% of the injected label of remnants and phospholipid-depleted chylomicrons was incorporated into the livers compared with less than 10% of the injected radioactivity of intact chylomicrons. A similar rapid hepatic uptake of radioactivity occurred when rats not pretreated with Triton were injected with [3H]cholesterol-labelled phospholipid-depleted chylomicrons. This rapid hepatic uptake of phospholipid-depleted chylomicrons occurred apparently without any alteration in the apoprotein composition of the particles. 2. The participation of hepatocytes in the uptake of remnants and phospholipid-depleted chylomicrons was examined. Both types of particles were taken up by the hepatocytes. However, small chylomicrons (Sf less than 400) were taken up more efficiently than were large chylomicrons (Sf greater than 400), but neither was taken up as efficiently as the remnants. 3. The results of this study lend support to the hypothesis that phospholipid-depleted chylomicrons and chylomicron remnants are taken up by the liver by a similar mechanism, which depends on the loss of surface phospholipids.

SUBMITTER: Borensztajn J

PROVIDER: S-EPMC1163576 | biostudies-other | 1981 Dec

REPOSITORIES: biostudies-other

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Project description:The aims of the present study were to evaluate the metabolism of chylomicrons (CM) and of CM remnants after labelling with radioactive iodine and converting the iodinated CM into remnants in vitro. Lymph CM were radiolabelled with 125I or sham-labelled with 127I by either the ICl procedure or the tyramine-cellobiose (TC) procedure, then injected into rats. The clearance from plasma of the iodinated CM was compared with control non-iodinated lipid-labelled CM. After iodination with ICl, the plasma removal of endogenously labelled CM was significantly different from non-iodinated CM, with increased uptake of CM triacylglycerols by the liver. In contrast, the clearances from plasma and the uptake by organs of radiolabelled lipids of CM iodinated by the TC method (TC-CM) were similar to control CM. About 40% of the label from 125I-TC-CM was insoluble in 50% propan-2-ol, indicating association with CM apolipoprotein B48. Only about 8% of label was lipid soluble, mostly in phosphatidylethanolamine. Radioactivity from 125I-TC-CM injected intravenously in rats was cleared rapidly and by 30 min only 20% remained in plasma, whereas 48% was recovered in the liver. After fractionation of the plasma by density-gradient ultracentrifugation, most label remained associated with d (relative density) less than 1.006 lipoproteins. In intact rats label was also found associated with the low-density and high-density lipoprotein fractions of plasma. When the liver was excluded from circulation, the recovery of label in low-density- and high-density-lipoprotein fractions was greatly decreased. CM remnants were prepared in vivo by injecting 125I-TC-CM into functionally hepatectomized donors and compared with remnants prepared in vitro by incubation with purified bovine milk lipoprotein lipase. Although remnants prepared in vitro cleared from plasma slower than remnants prepared in vivo, the size, lipid composition and apolipoprotein profile on gradient PAGE of the remnants were similar. We conclude that labelling of CM by the TC method avoided the 'artefactual' changes in metabolism seen after labelling by the ICl procedure. CM remnants when prepared in vitro using lipoprotein lipase were found to be similar to those prepared in vivo after injection into functionally hepatectomized rats.

Project description:Lipoprotein lipase (LPL) has been proposed to play a role in the uptake of chylomicron remnants by hepatocytes by mediating the binding of these lipoproteins to cell-surface glycosaminoglycans and to the low-density-lipoprotein receptor-related protein (LRP). This proposal is based on studies that examined the binding of chylomicrons to HepG2 cells, fibroblasts and Chinese hamster ovary cells in culture, in the presence of large amounts of LPL [Beisiegel (1995) Curr. Opin. Lipidol. 6, 117-122]. We have investigated whether LPL attached to the surface of chylomicrons enhances the binding and uptake of these lipoproteins to isolated hepatocytes maintained in culture. Bovine milk LPL was bound to mouse chylomicrons, double-labelled in vivo with [3H]retinol (in retinyl esters) and with [14C]palmitic acid (in triacylglycerols), collected from the mesenteric lymph of normal mice and from mice lacking the apoprotein E (apo E) gene. Normal chylomicrons (containing apo E) and apo E-free chylomicrons, with or without bound LPL, were incubated with cultured hepatocytes isolated from mice lacking the apo E gene. At 0 degree C LPL did not enhance the binding of the normal or apo E-free chylomicrons by the hepatocytes. When incubations were performed at 37 degrees C the triacylglycerols of normal and apo E-free chylomicrons were hydrolysed by LPL and there was a significant uptake of [14C]fatty acids and [3H]retinol by the hepatocytes. The addition of heparin or lactoferrin, a known inhibitor of hepatic uptake of chylomicron remnants, to the incubation medium inhibited the uptake of [3H]retinol, present in the lipoprotein core, but not the uptake of the [14C]fatty acids. We conclude that: (1) LPL attached to chylomicrons in amounts sufficient to effectively hydrolyse their core triacylglycerols does not enhance the binding of these lipoproteins to the surface of isolated hepatocytes; (2) the recognition and uptake of chylomicrons by hepatocytes requires that these lipoproteins be first hydrolysed by LPL; and (3) the uptake of lipolysed chylomicrons (remnants) by hepatocytes does not require the mediation of apo E.

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Hepatic uptake of phospholipid-depleted chylomicrons in vivo. Comparison with the uptake of chylomicron remnants.

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