Cholesterol esters selectively delivered in vivo by high-density-lipoprotein subclass LpA-I to rat liver are processed faster into bile acids than are LpA-I/A-II-derived cholesterol esters.
High-density lipoprotein (HDL) subclass LpA-I has been reported to promote cholesterol efflux from mouse adipose cells in vitro, whereas subclass LpA-I/A-II has no effect. To investigate whether the apolipoprotein composition of HDL plays a role in the selective delivery of cholesterol esters to the liver in vivo, we labelled HDL in its cholesterol ester moiety and separated [3H]cholesterol oleate-labelled HDL into subclasses LpA-I and LpA-I/A-II by immuno-affinity chromatography. Serum decay and liver association of LpA-I and LpA-I/A-II were compared for the apoprotein and cholesterol ester moieties. Both LpA-I and LpA-I/A-II selectively delivered cholesterol esters to the liver with similar kinetics. The kinetics of biliary secretion of processed cholesterol esters, initially associated with LpA-I or LpA-I/A-II, were studied in rats equipped with permanent catheters in bile, duodenum and heart. For both LpA-I and LpA-I/A-II, liver association was coupled to bile acid synthesis, with an increase in secretion rate during the night. During the first night period, the biliary secretion of LpA-I-derived radio-activity was significantly greater than for LpA-I/A-II. The data indicate that with both LpA-I and LpA-I/A-II selective delivery of cholesterol esters from HDL to the liver occurs, but that cholesterol esters delivered by LpA-I are more efficiently coupled to bile acid synthesis.
Pieters
M N
MN
Division of Biopharmaceutics, Sylvius Laboratory, University of Leiden, The Netherlands.
Castro
G R
GR
Schouten
D
D
Duchateau
P
P
Fruchart
J C
JC
Van Berkel
T J
TJ
D000818:Animals; D016633:Apolipoprotein A-II / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport; D002788:Cholesterol Esters / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D017270:Lipoprotein(a) / Q000031:analogs & derivatives* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000302:isolation & purification; D008099:Liver / Q000378:metabolism*; D008297:Male; D011865:Radioisotope Dilution Technique; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D016633:Apolipoprotein A-II; D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; D014316:Tritium; C078260:lipoprotein A-I