Binding of Apolipoproteins A to Adipose Cells : Role of Receptor Sites in Cholesterol Efflux and Purification of Binding Protein(S)

  • Ronald Barbaras
  • Pascal Puchois
  • Anne Pradines Figuères
  • Armin Steinmetz
  • Véronique Clavey
  • Nordine Ghalim
  • Jean-Charles Fruchart
  • Gèrard Ailhaud
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 285)


Epidemiological studies have shown a relationship between low concentrations of high density lipoprotein (HDL) cholesterol and the incidence risk of cardiovascular diseases1,2. Recent pharmacological studies3 have clearly demonstrated the protective role of HDL and their involvment in reverse cholesterol transport in vivo 4,5. In that respect apo E-free HDL has been long known to bind to a variety of cells and to promote cholesterol efflux6. Among peripheral tissues, adipose tissue is recognized both in man and rodents for its ability to accumulate, store and, when needed, mobilize a large pool of unesterified cholesterol7,8. Thus adipose cells represent a cell type suitable to study the first step in reverse cholesterol transport, i.e. cholesterol efflux. Unfortunately adipocytes isolated from adipose tissue loose their viability within a few hours, preventing the analysis of middle-term and long-term responses. During the last decade have been established in our laboratory preadipocyte cell lines from adipose tissue of genetically obese ob/ob mice9 and their lean counterpart10. The validity of these cellular models is supported by i) the biochemical properties of differentiated cells which are similar, if not identical, to those of adipocytes isolated from fat tissue and ii) the ability of undifferentiated cells to differentiate in vivo within a few weeks into fully mature fat cells after their injection into athymic mice, under conditions where these cells could be unambiguously demonstrated not to be fat cells originating from the host animal11.


Receptor Site Cholesterol Efflux Reverse Cholesterol Transport Adipose Cell Cholesterol Accumulation 
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  1. 1.
    T. Gordon, W.P. Castelli, M. C. Hjortland, W. B. Kannel and T. R. Dawber, High density lipoprotein as a protective factor agains coronary heart disease: the Frammingham Study, Am. J. Med. 62:707 (1977).PubMedCrossRefGoogle Scholar
  2. 2.
    N. E. Miller, O. H. Forde, D. S. Thelle and O. D. Mjos, The Tromso Heart Study: high-density lipoprotein and coronary heart disease: a prospective cas control study, Lancet 1:965 (1977).PubMedCrossRefGoogle Scholar
  3. 3.
    M. Heikki Frick et al., Helsinki heart study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidiema: safety or treatment, changes in risk factors, and incidence of coronary heart disease, N. Engl. J Med. 317:1237 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    N. E. Miller, A. La Ville and D. Crook, Direct evidence that reverse cholesterol transport is mediated by high density lipoprotein in rabbit, Nature 314:109 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    Th. J.C. van Berkel, H. F. Bakkeren, F. Kuipers and R. J. Vonk in : Proceedings of Xth International Symposium on Drugs Affecting Metabolism, p.47 (1989).Google Scholar
  6. 6.
    A. R. Tall and D. M. Small, Body cholesterol removal: role of plasma high-density proteins, Adv. Lipid Res. 17:1 (1980).PubMedGoogle Scholar
  7. 7.
    R. K. Krause and A. D. Hartman, Adipose tissue and cholesterol metabolism, J. Lipid Res. 25:97 (1984).PubMedGoogle Scholar
  8. 8.
    A. Angel and B. Fong, Lipoprotein interactions and cholesterol metabolism in human fat cells, in: The Adipocyte and Obesity: Cellular and Molecular Mechanisms, A. Angel, C. H. Hollenberg and D. A. K. Roncari, eds., Raven Press, New York (1983).Google Scholar
  9. 9.
    R. Negrel, P. Grimaldi and G. Ailhaud, Establishment of preadipocyte clonal line from epididymal fat pad ob/ob mouse that responds to insulin and to lipolytic hormones, Prc-c, Natl. Acad. Sci, USA 75:6054 (1978).CrossRefGoogle Scholar
  10. 10.
    C. Forest, A. Doglio, L. Casteilla, D. Ricquier andG. Ailhaud, Expression of the mitochondrial uncoupling protein in brown adipocytes. Absence in brown preadipocytes and BFC-1 cells. Modulation by isoproterenol in adipocytes, Exp. Cell Res. 168:233 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    D. Gaillard, P. Poli and R. Negrel, Characterization of ouabain-resistant mutants of the preadipocyte Obl7 clonal line. Adipose conversion in vitro and in vivo ,Exp, Cell Res. 156:513 (1985).CrossRefGoogle Scholar
  12. 12.
    R. Barbaras, P. Grimaldi, R. Négrel, and G. Ailhaud, Binding of lipoproteins and regulation of cholesterol synthesis in cultured mouse adipose cells, Biochim. Biophys. Acta 845:492 (1985).PubMedCrossRefGoogle Scholar
  13. 13.
    R. Barbaras, P. Grimaldi, R. Négrel, and G. Ailhaud, Characterization of high-density lipoprotein binding and cholesterol efflux in cultured mouse adipose cells, Biochim. Biophys. Acta 888:143 (1986).PubMedCrossRefGoogle Scholar
  14. 14.
    P. Forgez, M. J. Chapman, S. C. Rall Jr. and M. C. Camus, The lipid transport system in the mouse, Mus musculus isolation and characterization of apolipoproteins B, AI, All, and CIII, J. Lipid Res. 25:954 (1984).PubMedGoogle Scholar
  15. 15.
    C. G. Miller, T. D. Lee, R. C. LeBoeuf and J. E. Shively, Primary structure of apolipoprotein All from inbred mouse strain BALB/c, J. Lipid Res. 28:311 (1987).PubMedGoogle Scholar
  16. 16.
    S. C. Williams, S. M. Bruckheimer, A. J. Lusis, R. C. LeBoeuf and A. J. Kinniburgh, Mouse apolipoprotein AIV gene: nucleotide sequence and induction by a high-lipid diet, Mol. Cell. Biol. 6:3807 (1986).PubMedGoogle Scholar
  17. 17.
    T. L. Innerarity, E. J. Friedlander, S. C. Rall,K. H. Weisgarber and R. W. Mahley, The receptor-binding domain of human apolipoprotein E, J. Biol. Chem258:12341 (1983).PubMedGoogle Scholar
  18. 18.
    T. J. Knott, R. J. Pease, L. M. Powell, S. C. Wallis, S. C. Rall Jr., T. L. Innerarity, B. Blankhart, W. H. Taylor, Y. Marcel, R. W. Mahley, B. Levy-Wilson and J. Scott, Complete protein sequence and identification of structural domains of human apolipoprotein B, Nature 323:734 (1986).PubMedCrossRefGoogle Scholar
  19. 19.
    C. Y. Yang, S. H. Chen, S. H. Gianturco, W. A. Bradley, J. T. Sparrow, M. Tanimura, W. K. Li, D. A. Sparrow, H. DeLoof, M. Rosseneu, F. S. Lee, Z. W. Gu, A. M. Gotto Jr. and L. Chan, Sequence, structure, receptor binding domains and internal repeats of human apolipoprotein B-100, Nature 323:738 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    A. J. Lusis, R. West, M. Mehrabian, M. A. Reuben, R. C. LeBoeuf, J. S. Kaptein, D. F. Johnson, V. N. Schumaker, M. P. Yuhasz, M. C. Schotz and J. Elovson, Cloning and expression of apolipoprotein B, the major protein of low and very low density lipoproteins, Proc. Natl. Acad. Sci. USA 82:4597 (1985).PubMedCrossRefGoogle Scholar
  21. 21.
    A. Steinmetz, R. Barbaras, N. Ghalim, V. Clavey, J.C. Fruchart, and G. Ailhaud, Human apolipoprotein AIV binds to apolipoprotein AI/AII receptor sites and promotes cholesterol efflux from adipose cells, J. Biol. Chem. 265:7859 (1990).PubMedGoogle Scholar
  22. R. Barbaras, P. Puchois, J.C. Fruchart, A. Pradines-Figueres and G. Ailhaud, Purification of the apolipoprotein A receptor from mouse adipose cells, Biochem. J., in press.Google Scholar
  23. 23.
    R. Barbaras, P. Puchois, J.C. Fruchart and G. Ailhaud, Cholesterol efflux from cultured adipose cells is mediated by LpAI particles and not by LpaI:AII particles, Biochem. Biophys. Res. Commun. 142:63 (1987) .PubMedCrossRefGoogle Scholar
  24. 24.
    R. Barbaras, P. Puchois, P. Grimaldi, A. Barkia, J.C. Fruchart and G. Ailhaud, in: Eicosanoids, Apolipoproteins, Lipoprotein Particles, and Atherosclerosis, C. L. Malmendier and P. Alaupovic, eds., Plenum Press, New York (1988).Google Scholar
  25. 25.
    P. Grimaldi, D. Czerucka, M. Rassoulzadegan, F. Cuzin and G. Ailhaud, Obl7 cells transformed by middle-T-only gene of polyoma virus differentiate in vitro and in vivo into adipose cells, Proc. Natl. Acad. Sci. USA 81:5440 (1984) .PubMedCrossRefGoogle Scholar
  26. 26.
    R. Barbaras, P. Puchois, P. Grimaldi, A. Barkia, J.C. Fruchart and G. Ailhaud, Relationship in adipose cells between the presence of receptor sites for high density lipoproteins and the promotion of reverse cholesterol transport, Biochem. Biophys. Res. Commun149:545 (1987).PubMedCrossRefGoogle Scholar
  27. 27.
    C. Delbart, N. Théret, G. Ailhaud, J.C. Fruchart, Phosphatidylcholine breakdown during receptor binding of HDL3, Circulation 80:487 (1989).Google Scholar
  28. A. Barkia, P. Puchois, N. Ghalim, R. Barbaras, G. Ailhaud and J.C. Fruchart, Differential role of apolipoprotein Al-containing particles in cholesterol efflux from adipose cells, submitted.Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Ronald Barbaras
    • 1
  • Pascal Puchois
    • 2
  • Anne Pradines Figuères
    • 1
  • Armin Steinmetz
    • 2
  • Véronique Clavey
    • 2
  • Nordine Ghalim
    • 2
  • Jean-Charles Fruchart
    • 2
  • Gèrard Ailhaud
    • 1
  1. 1.Centre de BiochimieParc ValroseNiceFrance
  2. 2.SERLIAInstitut PasteurLilleFrance

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