We have previously shown that bile duct
ligation inhibits the hepatic uptake of
chylomicron remnants in rats. In the present study we have investigated different possible causes of this inhibition.
Intravenous infusion of bile or
sodium taurocholate reduced the hepatic
chylomicron remnant uptake. Perfused livers from bile duct-ligated rats metabolized
chylomicron remnants at a reduced rate. Rat hepatocyte monolayer cultures metabolized remnants formed in cholestatic rats and those formed in hepatectomized animals equally well, but serum from cholestatic rats inhibited remnant uptake more strongly than control serum. Bile duct
ligation did not influence the clearance from plasma of human
low-density lipoprotein, and the inhibition of hepatic remnant uptake was not affected by treatment of cholestatic rats with ethinylestradiol. The clearance of 125I-labeled
asialofetuin was only slightly impaired by
cholestasis, indicating that no strong inhibition of all endocytic processes of the hepatocytes occurred. The reduced hepatic uptake of
chylomicron remnants in the cholestatic rat is thus not due to formation of abnormal remnant particles. An increased plasma
bile acid concentration rapidly reduced the hepatic remnant uptake without causing any significant
hyperlipidemia. However, the pathological
lipoproteins accumulating in the cholestatic rat aggravated the hepatic uptake defect even further.