, Volume 28, Issue 8, pp 709–713 | Cite as

Bile acid and very low density lipoprotein production by cultured hepatocytes from hypo- orhyperresponsive rabbits fedcholesterol

  • Evgeniy A. Podrez
  • Vladimir A. Kosykh
  • Yuri V. Lakeev
  • Evgeniy I. Kosenkov
  • Elvira T. Mambetisaeva
  • Vadim S. Repin
  • Vladimir N. Sminov
  • Tatu A. Miettinen


Two groups of rabbits, either hyperresponsive or hyporesponsive to dietary cholesterol, wereselected after ten weeks of cholesterol feeding (0.2 g cholesterol/kg body weight per day). Bile acids and very low density lipoprotein (VLDL) production were determined in primary hepatocyte cultures from control, hyper- and hyporesponsive rabbits. Free cholesterol and cholesteryl ester contents in hepatocytes of the hyperresponsive rabbits was significantly increased. In contrast, lipid composition in hepatocytes of the hyporesponders was similar to that of control cells. Cholic acid was the predominant bile acid in the culture medium of hepatocytes together with small amounts of chenodeoxycholic and deoxycholic acids. The rate of cholic acid production by hepatocytes in the hyporesponsive group was two times higher than that in the hyperresponsive group. Bile acid production by control hepatocytes was slightly higher than in the hyperresponsive group. In contrast, secretion of VLDL cholesteryl ester was significantly increased by hepatocytes of the hyperresponsive rabbits. Similar differences, in bile acid production were found between hypo- and hyperresponsive rabbits selected after five days of cholesterol feeding and subsequent maintenance on a low cholesterol diet for a period of one month. The results suggest that the increased rate of bile acid production could contribute to the apparent resistance of hyporesponders to the atherogenic diet.



apoprotein B and apoprotein E


fetal bovine serum


gas-liquid chromatography


high-performance thin-layer chromatography


Eagle's minimum essential medium


very low density lipoprotein


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  1. 1.
    Roberts, D.C.K., West, C.E., Redgrave, T.G., and Smith, J.B. (1974)Atherosclerosis 19, 369–380.PubMedCrossRefGoogle Scholar
  2. 2.
    Van Zutphen, L.F.M., Den Bieman, M.G.C.W., Hülsman, W.C., and Fox, R.R. (1981)Lab. Animals 15, 61–67.Google Scholar
  3. 3.
    Beynen, A.C., Katan, M.B., and Van Zutphen, L.F.M. (1987)Adv. Lipid Res. 22, 115–125.PubMedGoogle Scholar
  4. 4.
    Lofland, Jr., H.B., Clarkson, T.B., St. Clair, R.W., and Lehner, N.D.M. (1972)J. Lipid Res. 13, 39–47.PubMedGoogle Scholar
  5. 5.
    Beynen, A.C., Meijer, G.W., Lemmens, A.G., Glatz, J.F.C., Versluis, A., Katan, M.B., and Van Zutphen, L.F.M. (1989)Atherosclerosis 77, 151–157.PubMedCrossRefGoogle Scholar
  6. 6.
    Overturf, M.L., Smith, S.A., Gotto, A.M., Morrisett, J.D., Tewson, T., Poorman, J., and Loose-Mitchel, D.S. (1990).J. Lipid Res. 31, 2019–2027.PubMedGoogle Scholar
  7. 7.
    Kern, F. (1991)N. Engl. J. Med. 324, 896–900.PubMedCrossRefGoogle Scholar
  8. 8.
    Shore, V.G., Shore, B., and Hart, R.G. (1974)Biochemistry 13, 1579–1587.PubMedCrossRefGoogle Scholar
  9. 9.
    Roth, R.J., Gaubatz, J.W., Gotto., A.M., and Patsch, J.R. (1983)J. Lipid Res. 24, 1–11.PubMedGoogle Scholar
  10. 10.
    Mackinnon, A.M., Savage, J., Gibson, R.A, and Barter, P.J., (1985)Atherosclerosis 54, 145–155.PubMedCrossRefGoogle Scholar
  11. 11.
    Whiting, M.J., Wishart, R.A., Gowing, M.R., McManus, M.E., and Mackinnon, A.M. (1989)Biochim. Biophys. Acta 1001, 176–184.PubMedGoogle Scholar
  12. 12.
    Davis, R.A., Highsmith, W.E., Malone-McNeal, M.M., Schexnayder, J.A., and Kuan, J.-C.W. (1983)J. Biol. Chem. 258, 4079–4082.PubMedGoogle Scholar
  13. 13.
    Hylemon, P.B., Gurly, E.C., Kubaska, W.M., Whitehead, T.R., Guzelian, P.S., and Vlahcevic, Z.R. (1985)J. Biol. Chem. 260, 1015–1019.PubMedGoogle Scholar
  14. 14.
    Ford, R.P., Botham, K.M., Suckling, K.E., and Boyd, G.S. (1985)Biochim. Biophys. Acta 836, 185–191.PubMedGoogle Scholar
  15. 15.
    Reese, J.A., and Byard, J.L. (1981)In Vitro 17, 935–940.PubMedGoogle Scholar
  16. 16.
    Kosykh, V.A., Lankin, V.Z., Podrez E.A., Novikov, D.K., Volgushev, S.A., Victorov, A.V., Repin, V.S., and Smirnov, V.N. (1989),Lipids 24, 109–116.PubMedCrossRefGoogle Scholar
  17. 17.
    Grundy, S.M., Ahrens, Jr., E.H., and Miettinen, T.A. (1965)J. Lipid Res. 6, 397–410.PubMedGoogle Scholar
  18. 18.
    Miettinen, T.A., Ahrens, Jr., E.H., and Grundy, S.M. (1965)J. Lipid Res. 6, 411–424.PubMedGoogle Scholar
  19. 19.
    Miettinen, T.A. (1982)Clin.CChim. Acta 124, 245–248.CrossRefGoogle Scholar
  20. 20.
    Kallner, A. (1967)Acta Chem. Scand. 21, 322–328.PubMedGoogle Scholar
  21. 21.
    Bligh, E.C., and Dyer, W.J. (1959)Can. J. Biochem. Biophys. 37, 911–917.Google Scholar
  22. 22.
    Kempen, H.J.M., Vos van Holstein, M.P.M., and De Lange, J. (1982)J. Lipid Res. 23, 823–830.PubMedGoogle Scholar
  23. 23.
    Goldstein, J.L., Basu, S.K., and Brown, M.S. (1983)Methods Enzymol. 98, 241–260.PubMedGoogle Scholar
  24. 24.
    Schmitz, G., Assmann G., and Bowyer, D.E. (1984)J. Chromatogr. 307, 65–80.PubMedGoogle Scholar
  25. 25.
    Schmitz, G., Lenczyk, M., Ord, D., Bowyer, D.E., and Assmann, G. (1984)J. Chromatogr. 307, 81–89.PubMedGoogle Scholar
  26. 26.
    Shore, B., and Shore, V.K. (1976) inAtherosclerosis Drug Discovery (Day, C.E., ed.) pp. 123–141, Plenum Press, New York.Google Scholar
  27. 27.
    Kosykh, V.A., Podrez, E.A., Novikov, D.K., Dolbin, A.G., Repin, V.S., and Smirnov, V.N. (1987)Atherosclerosis 10, 67–76.CrossRefGoogle Scholar
  28. 28.
    Bhattacharyya, A.K., and Eggen, D. (1981)J. Lipid Res. 22, 16–23.PubMedGoogle Scholar
  29. 29.
    Katan, M.B., and Beynen, A.C. (1987)Am. J. Epidemiology 125, 387–399.Google Scholar
  30. 30.
    Dory, L., Bhattacharyya, A., Strong, J., and Chappius, C. (1990)J. Lipid Res., 31, 279–285.PubMedGoogle Scholar
  31. 31.
    Kesaniemi, Y.A., and Miettinen, T.A. (1987)Eur. J. Clin. Invest. 17, 391–395.PubMedCrossRefGoogle Scholar
  32. 32.
    Hulcher, F.H., and Margolis, R.D. (1982)Biochim. Biophys. Acta 712, 242–249.PubMedGoogle Scholar
  33. 33.
    Stange, E.F., Scheibner, J., and Ditschuneit, H. (1989)J. Clin. Invest. 84, 173–180.PubMedGoogle Scholar
  34. 34.
    Heuman, D.M., Hylemon, P.B., and Vlahcevic, Z.R. (1989)J. Lipid Res. 30, 1161–1167.PubMedGoogle Scholar
  35. 35.
    Hall, R., Kok, E., and Javitt, N.B. (1988)FASEB J. 2, 152–156.PubMedGoogle Scholar
  36. 36.
    Loose-Mitchel, D.S., Poorman, J.A., Smith, S.A., Overturf, M.L., Morrisett, J.D., Gotto, A.M., and Soma, M.R. (1991)Atherosclerosis 87, 169–181.CrossRefGoogle Scholar

Copyright information

© American Oil Chemists’ Society 1993

Authors and Affiliations

  • Evgeniy A. Podrez
    • 1
  • Vladimir A. Kosykh
    • 1
  • Yuri V. Lakeev
    • 1
  • Evgeniy I. Kosenkov
    • 1
  • Elvira T. Mambetisaeva
    • 1
  • Vadim S. Repin
    • 1
  • Vladimir N. Sminov
    • 1
  • Tatu A. Miettinen
    • 2
  1. 1.Cardiology Research CenterAcademy of Medical SciencesMoscowRussia
  2. 2.Second Department of MedicineUniversity of HelsinkiHelsinkiFinland

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