In Vitro Binding and in Vivo Uptake of Chylomicron Remnants after their Hydrolysis by Hepatic Lipase

  • Fabrice Sultan
  • Dominique Lagrange
  • Sabine Griglio
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 285)


Chylomicron remnants (CM-RM), resulting from intravascular hydrolysis of chylomicrons by the endothelium bound lipoprotein lipases (LPL), are rapidly taken up by the liver. It appears clearly that this uptake is mostly receptor mediated1–3 and that CM-RM are taken up as whole particles. Hepatic lipase (HL), which exerts both a triacylglycerol lipase and phospholipase Al activity, may be involved in with CM-RM uptake. Indeed, its inhibition by a specific anti-HL antibody leads to an accumulation of apo B-48 rich-par ticles in the plasma of rats4,5. We have previously shown that CM-RM prealably hydrolyzed by HL and then added to isolated hepatocytes are taken up at a higher rate than non-treated remnants (6). Moreover, we showed that following hydrolysis by HL, there was no modification in remnant apo E levels (unpublished results). Since apo E is the ligand for remnant binding to their hepatic receptors1–3, we examined herein, whether HL-treatment of CM RM could despite unchanged apo E levels, increase 1) the binding of such particles to liver membranes and 2) their plasma clearance and hepatic uptake in vivo.


Cholesteryl Ester Hepatic Uptake Hepatic Lipase Liver Plasma Membrane Chylomicron Remnant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    E.E.T. Windier, Y.S. Chao and R.J. Havel. Regulation of the hepatic uptake of triglyceride -rich lipoproteins in the rat. Opposing effects of homologous apolipoprotein E and individual C apolipoproteins, J. Biol. Chem. 255:8303 (1980).Google Scholar
  2. 2.
    A.D. Cooper, S.K. Erickson, S.K., R. Nutik and M.A. Shrewsbury. Characterization of chylomicron remnants binding to rat liver mem branes, J. Lipid Res. 23:42 (1982).PubMedGoogle Scholar
  3. 3.
    R.W. Mahley, D.Y. Hui, T.L. Innerarity and U. Beisigel. Chylomicron remnant metabolism. Role of hepatic lipoprotein receptors in mediaring uptake, Arteriosclerosis 9 (1):14 (1989).Google Scholar
  4. 4.
    P.B. Daggy and A. Bensadoun. Enrichment of apolipoprotein B-48 in the LDL density class following in vivo inhibition of hepatic lipase, Biochim. Biophys. Acta 877:252 (1986).PubMedGoogle Scholar
  5. 5.
    F. Sultan, D. Lagrange, H. Jansen and S. Griglio. Inhibition of hepa tic lipase activity impairs chylomicron remnant removal in rats, Biochim. Biophys. Acta, 1042:150 (1990).PubMedGoogle Scholar
  6. 6.
    F. Sultan, D. Lagrange, X. Le Liepvre and S. Griglio. Chylomicron remnant uptake by freshly isolated hepatocytes. Effect of heparin and of triacylglycerol lipase, Biochem. J., 258:587 (1989).PubMedGoogle Scholar
  7. 7.
    A. Van Tol, T. Van Gent and H. Jansen. Degradation of HDL by heparin releasable liver lipase, Biochem. Biophys. Res. Commun. 94:101 (1980).PubMedCrossRefGoogle Scholar
  8. 8.
    K. Schoonderwoerd, W.C. Hiilsmann and H. Jansen. Regulation of liver lipase. Evidence for several regulatory sites studied in corticotrophin-treated rats, Biochim. Biophys. Acta 754:279 (1983).PubMedGoogle Scholar
  9. 9.
    D.W. Bilheimer, S. Eisenberg and R.I. Levy. The metabolism of VLDL proteins. Preliminary in vitro and in vivo observations, Biochim. Biophys. Acta 260:212 (1972).PubMedGoogle Scholar
  10. 10.
    T.K. Ray. A modified method for the isolation of the plasma membrane from rat liver. Biochim. Biophys. Acta 196:1 (1970).PubMedCrossRefGoogle Scholar
  11. 11.
    D.H. Lowry, N.J. Rosebrough, A.L. Farr and R.J. Randal. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265 (1951).PubMedGoogle Scholar
  12. 12.
    Y. Nagata, J. Chen, and A.D. Cooper. Role of LDL-receptor dependent and independent sites in binding and uptake of chylomicron-remnants in rat liver. J. Biol. Chem. 263:15151 (1988).PubMedGoogle Scholar
  13. 13.
    E. Jensen, C.H. Floren and A. Nilsson. Cell density dependent uptake of chylomicron-remnants in rat hepatocyte monolayers. Effects of compact in and mevalonic acid. Biochim. Biophys. Acta 917:74 (1987)PubMedGoogle Scholar
  14. 14.
    E.E.T. Windier, J. Greeve, W. Daerr and H. Greten. Binding of rat chylomicrons and their remnants to the LDL receptor and its role in remnant removal. Biochem. J. 252:553 (1988).Google Scholar
  15. 15.
    J. Hertz, V. Hamann, S. Rogne, 0. Myklebost, H. Gausepohl and K.K. Stanley. Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor, EMBO J., 7:4119 (1988).Google Scholar
  16. 16.
    S. Jeackle, S.E. Brady and R.J. Havel. Membrane binding sites for plasma lipoproteins on endosomes from rat liver. Proc. Natl. Acad. Sci. 86:1880 (1989).CrossRefGoogle Scholar
  17. 17.
    A.D. Cooper. The metabolism of chylomicron-remnants by isolated perfused rat liver. Biochim. Biophys. Acta 488:464 (1977).PubMedGoogle Scholar
  18. 18.
    P.M. Lippiello, P.J. Sisson and M. Waite. The uptake and metabolism of chylomicron-remnants by rat liver parenchymal and non-parenchymal cells in vitro. Biochem. J. 232:395 (1985).PubMedGoogle Scholar
  19. 19.
    Y. Oschry and S. Eisenberg. Rat plasma lipoprotein:reevaluation of a lipoprotein system in an animal devoid of cholesteryl ester transfer activity. J. Lipid. Res. 23:1099 (1982).PubMedGoogle Scholar
  20. 20.
    J.C. Gibson and W.V. Brown. Effect of lipoprotein lipase and hepatic triglyceride lipase activity on the distribution of apolipoprotein E among the plasma lipoproteins. Atherosclerosis 73:45 (1988).PubMedCrossRefGoogle Scholar
  21. 21.
    J. Borensztajn, G.S. Getz and T.J. Kotlar. Uptake of chylomicron remnants by the liver:further evidence for the modulating role of phospholipids. J. Lipid Res. 29:1987 (1988).Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Fabrice Sultan
    • 1
  • Dominique Lagrange
    • 1
  • Sabine Griglio
    • 1
  1. 1.Physiopathologie de la NutritionINSERM U.177Paris Cedex 06France

Personalised recommendations