Bile acid-lipoprotein interactions: effects of ursodeoxycholic acid (ursodiol)

Several studies in the hamster model were undertaken to investigate known and recently disclosed metabolic interactions between bile acids and lipoproteins, particularly between ursodiol and low-density-lipoprotein (LDL) receptors. Three groups of animals, receiving a control 0.027% cholesterol diet, supplementation with 0.1% ursodiol, or supplementation with 0.1% chenodeoxycholic acid, were treated for four weeks. Both bile acids suppressed bile acid synthesis. Chenodeoxycholic acid significantly increased serum total cholesterol compared to ursodiol, and high-density-lipoprotein (HDL) cholesterol decreased significantly with chenodeoxycholic acid compared to ursodiol and control. Since the rate of bile acid synthesis is known to influence LDL receptor activity, LDL uptake under these conditions of synthesis suppression was measured. The animals received infusions of hamster LDL and methylated human LDL. Uptake of hamster LDL (occurring by both receptor-dependent and receptor-independent mechanisms) was significantly higher in the ursodiol-treated group than in the others. Human LDL uptake (occurring only by receptor-independent mechanisms) was not significantly affected by either treatment. The mechanisms by which ursodiol apparently directly stimulates the LDL receptor remain speculative but may involve alteration of cell membrane fluidity, change in the rate of LDL receptor cycling, and increase in the number of LDL receptors.