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Studies on the mechanism of the ursodeoxycholic acid‐induced increase in hepatic low‐density lipoprotein binding
Author(s) -
Bouscarel Bernard,
Caryak Susan,
Robins Sander J.,
Fromm Hans
Publication year - 1995
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536997
Subject(s) - ursodeoxycholic acid , chenodeoxycholic acid , medicine , chemistry , endocrinology , lipoprotein , low density lipoprotein , bile acid , hamster , ldl receptor , receptor , cholesterol , incubation , catabolism , biochemistry , metabolism , biology
Previously, we have shown, in golden Syrian hamsters, that chronic feeding of ursodeoxycholic acid (UDCA), in contrast to that of its 7α‐epimer, chenodeoxycholic acid (CDCA), produced a significant increment in hepatic low‐density lipoprotein (LDL) uptake, despite similar suppression of bile acid synthesis by both bile acids. Evidence for a direct effect of this bile acid on hepatic LDL metabolism was shown in vitro , with isolated hamster hepatocytes, suggesting that this effect was unique to UDCA and specific for receptor‐mediated LDL catabolism. The aim of the present study was to define the cellular mechanism(s) associated with this phenomenon, using male golden Syrian hamsters. Regardless of chronic exposure of the liver to either UDCA or CDCA, acute incubation with UDCA consistently resulted in an increase of LDL binding to isolated hepatocytes by 15 to 40%. Furthermore, chronic treatment with either UDCA or CDCA did not result in alterations in lipoprotein particle composition. Likewise, incubation of hepatocytes with UDCA was not associated with a change of the membrane lipid composition. In isolated liver membrane fractions, UDCA increased both the maximum number of LDL binding sites and the affinity constant for LDL by around 35% suggesting an interaction of UDCA with the LDL receptor, at the plasma membrane level, independent of an effect on receptor cycling. The results of the studies support a role for UDCA in the recruitment of cryptic LDL receptors from a cellular membrane pool, possibly due to the unique localization of UDCA in the plasma membrane lipid bilayer.