Inhibition of Hepatic Chylomicron Remnant Uptake in the Cholestatic Rat

Abstract

[³H]retinol- or [³H]cholesterol- and [¹⁴C]fatty acid-labeled chylomicrons and chylomicron remnants were injected intravenously into normal rats and rats subjected to partial or total obstruction of the bile duct 8 or 48 h earlier. The clearance from plasma of the [³H]retinyl and the [³H]cholesteryl esters in 30–120 min was markedly decreased in rats with total obstruction, and the uptake of ³H by the liver was significantly less than in control rats. The elimination of the [¹⁴C]triacylglycerol of the native chyle lipoprotein was not significantly affected, and the delayed plasma clearance was seen also when the [³H]lipid ester radioactivity was injected as chylomicron remnants prepared in vitro. If only one of the two main bile duct branches was ligated, the uptake of radioactivity did not differ markedly in the obstructed and unobstructed part of the liver, and only small effects on the plasma disappearance were seen. The defective clearance of the chylomicron remnants was thus not related to the obstructed bile flow per se but rather to the consequences of the total obstruction, such as the high plasma bile acid level or the accumulation of abnormal lipoproteins in plasma.

Key-words:

• Bile acids
• cholestasis
• cholesteryl ester
• chylomicron
• chylomicron remnant
• retinyl ester