Selective uptake of cholesteryl esters from apolipoprotein-E-free high-density lipoproteins by rat parenchymal cells in vivo is efficiently coupled to bile acid synthesis.
[3H]Cholesteryl ester-labelled human high-density lipoprotein (HDL) was injected into rats and its decay, intrahepatic cellular distribution and the kinetics of biliary secretion were determined. At 10 min after injection the hepatic uptake of cholesteryl esters from HDL was 3-fold higher as compared with the apolipoprotein. Selective uptake was exerted only by parenchymal cells (5.6-fold more cholesteryl esters than apolipoprotein) and not by liver endothelial or Kupffer cells. The kinetics of biliary secretion of processed cholesteryl esters initially associated with HDL or low-density lipoprotein (LDL) were compared in unrestrained rats, equipped with permanent catheters in bile duct, duodenum and heart. At 72 h after injection of [3H]cholesteryl oleate-labelled HDL, 51.0 +/- 2.5% of the injected dose was recovered as bile acids, which is about twice as high as the secretion of biliary radioactivity after injection of [3H]cholesteryl oleate-labelled LDL. Oestradiol treatment stimulated only liver uptake of LDL cholesteryl esters, and resulted in a 2-fold higher liver uptake than with HDL. However, the rate of radioactive bile acid formation from [3H]cholesteryl oleate-labelled HDL was still more rapid than for LDL. It is concluded that the selective uptake pathway for cholesteryl esters from HDL in parenchymal cells is more efficiently coupled to the formation of bile acids than is the cholesteryl ester uptake from LDL. This efficient coupling may facilitate the role of HDL in reverse cholesterol transport.
Pieters
M N
MN
Division of Biopharmaceutics, Sylvius Laboratory, University of Leiden, The Netherlands.
Schouten
D
D
Bakkeren
H F
HF
Esbach
B
B
Brouwer
A
A
Knook
D L
DL
van Berkel
T J
TJ
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002788:Cholesterol Esters / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051381:Rats
D001057:Apolipoproteins E; D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D004958:Estradiol