Effects of Partial Ileal Bypass Surgery on Low-Density Lipoprotein Metabolism in Watanabe Heritable Hyperlipidemic Rabbits

  • Marc J. T. M. Mol
  • Anton F. H. Stalenhoef
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Partial ileal bypass (PIB) in Watanabe heritable hyperlipidemic rabbits (WHHL) causes a reduction in plasma cholesterol (chol) of approximately 50%. We have previously performed turnover studies of radiolabeled native and methylated LDL, which showed a reduction in the absolute catabolic rate (ACR) of LDL of 50% after PIB, whereas the fractional catabolic rate (FCR) was unchanged. Furthermore, the receptor-mediated clearance of LDL after PIB remained essentially zero. Use was made of nonautologous LDL from control (C) WHHL. We have now used LDL both from PIB WHHL and C WHHL to study the possible influence of PIB on the composition and kinetics of LDL; for this purpose, LDL was isolated from pooled serum of five WHHL (age 40 ± 4 weeks) 17 weeks after PIB and from pooled serum of five C WHHL (age 46 ± 2 weeks), labeled with 125I and 131I, respectively, and injected simultaneously into each of the ten animals and into one New Zealand white rabbit (NZW). Plasma radioactivities were followed for 72 hr. In PIB WHHL, the plasma pools of LDL-chol and apo LDL were considerably lower ( -82% and -67% versus C WHHL, respectively). Composition studies of LDL showed a significant decrease in cholesteryl esters (% mass) of 46% and a significant increase of triglycerides (% mass) of 120%. In contrast to our previous study, a significantly higher FCR of C LDL in PIB versus C WHHL was found. In addition, the FCR of PIB LDL was significantly higher than that of C LDL in both PIB and C animals. The FCR of PIB LDL in PIB WHHL was 1.5 times higher than the FCR of C LDL in C WHHL. The ACR of PIB LDL in PIB WHHL was 50% lower than the ACR of C LDL in C WHHL, confirming a decreased production rate of LDL after PIB. Our conclusions are: (1) PIB reduced the production rate of LDL, which is in accordance with the results of our previous studies; (2) PIB increased FCR of LDL, which was even more pronounced for PIB LDL (+ 507c) than for C LDL (+ 38%). The dual effect of PIB on production rate and FCR explains the large reduction in LDL. The increase in FCR is apparently caused by an increased uptake of LDL by the liver after PIB and also by intrinsic changes in the structure of LDL. In vitro studies are currently underway to investigate the mechanism of this enhanced uptake.


Cholesteryl Ester Familial Hypercholesterolemia Fractional Catabolic Rate WHHL Rabbit Partial Ileal Bypass 
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. Bilheimer, D. W., Grundy, S. M., Brown, M. S., and Goldstein, J. L., 1983, Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes, Proc. Natl. Acad. Sci. U.S.A. 80:4124–4128.PubMedCrossRefGoogle Scholar
  2. Dietschy, J. M., Kita, T., Suckling, K. E., Goldstein, J. L., and Brown, M. S., 1983, Cholesterol synthesis in vivo and in vitro in the WHHL rabbit, an animal with defective low density lipoprotein receptors, J. Lipid Res. 24:469–480.PubMedGoogle Scholar
  3. Goldstein, J. L., Kita, T., and Brown, M. S., 1983, Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia, N. Engl. J. Med. 309:288–296.PubMedCrossRefGoogle Scholar
  4. Kita, T., Brown, M. S., Bilheimer, D. W., and Goldstein, J. L., 1982a, Delayed clearance of very low density and intermediate density lipoproteins with enhanced conversion to low density lipoprotein in WHHL rabbits, Proc. Natl. Acad. Sci. U.S.A. 79:5693–5697.PubMedCrossRefGoogle Scholar
  5. Kita, T., Goldstein, J. L., Brown, M. S., Watanabe, Y., Hornick, C. A., and Havel, R. J., 1982b, Hepatic uptake of chylomicron remnants in WHHL rabbits: A mechanism genetically distinct from the low density lipoprotein receptor, Proc. Natl. Acad. Sci. U.S.A. 79:3623–3627.PubMedCrossRefGoogle Scholar
  6. Niekerk, J. L. M., van, Demacker, P. N. M., Hendriks, T., and de Boer, H. H. M., 1983, Partial ileal bypass inhibits atherosclerosis in WHHL rabbits, Atherosclerosis 48:243–252.PubMedCrossRefGoogle Scholar
  7. Niekerk, J. L. M. van, Hendriks, T., and de Boer, H. H. M., 1984, Bile acid drainage by partial small bowel bypass or cholestyramine: Effects on serum cholesterol in Watanabe heritable hyperlipidemic rabbits, Eur. Surg. Res. 16:282–287.PubMedCrossRefGoogle Scholar
  8. Schneider, W. J., Brown, M. S., Goldstein, J. L., 1983, Kinetic defects in the processing of the LDL receptor in fibroblasts from WHHL rabbits and a family with familial hypercholesterolemia, Mol. Biol. Med. 1:355–367.Google Scholar
  9. Stalenhoef, A. F. H., van Niekerk, J. L. M., Demacker, P. N. M., and van Laar, A., 1984, Partial ileal bypass reduces the production rate of low density lipoproteins in Watanabe heritable hyperlipidemic rabbits, J. Lipid Res. 25:1350–1357.Google Scholar
  10. Witztum, J. L., Young, S. G., Elam, R. L., Carew, T. E., and Fisher, M., 1985, Cholestyramine -induced changes in low density lipoprotein composition and metabolism. I. Studies in the guinea pig, J. Lipid Res. 26:92–103.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Marc J. T. M. Mol
    • 1
  • Anton F. H. Stalenhoef
    • 1
  1. 1.Department of Medicine, Division of General Internal MedicineSt. Radboud University HospitalNijmegenThe Netherlands

Personalised recommendations