Effects of Partial Ileal Bypass Surgery on Low-Density Lipoprotein Metabolism in Watanabe Heritable Hyperlipidemic Rabbits
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.
KeywordsCholesteryl Ester Familial Hypercholesterolemia Fractional Catabolic Rate WHHL Rabbit Partial Ileal Bypass
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