Hepatic uptake and metabolism of phosphatidylcholine associated with high density lipoproteins.
BACKGROUND
Phosphatidylcholine (PC) is the predominant phospholipid associated with high density lipoproteins (HDL). Although the hepatic uptake of cholesteryl esters from HDL is well characterized, much less is known about the fate of PC associated with HDL. Thus, we investigated the uptake and subsequent metabolism of HDL-PC in primary mouse hepatocytes.


RESULTS
The absence of scavenger receptor-BI resulted in a 30% decrease in cellular incorporation of [(3)H]PC whereas [(3)H]cholesteryl ether uptake was almost completely abolished. Although endocytosis is not involved in the uptake of cholesteryl esters from HDL, we demonstrate that HDL internalization accounts for 40% of HDL-PC uptake. Extracellular remodeling of HDL by secretory phospholipase A(2) significantly enhances HDL lipid uptake. HDL-PC taken up by hepatocytes is partially converted to triacylglycerols via PC-phospholipase C-mediated hydrolysis of PC and incorporation of diacylglycerol into triacylglycerol. The formation of triacylglycerol is independent of scavenger receptor-BI and occurs in extralysosomal compartments.


CONCLUSIONS
These findings indicate that HDL-associated PC is incorporated into primary hepatocytes via a pathway that differs significantly from that of HDL-cholesteryl ester, and shows that HDL-PC is more than a framework molecule, as evidenced by its partial conversion to hepatic triacylglycerol.
Robichaud
Julie C
JC
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
van der Veen
Jelske N
JN
Yao
Zemin
Z
Trigatti
Bernardo
B
Vance
Dennis E
DE
D000818:Animals; D011992:Endosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D007476:Ionophores / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008985:Monensin / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D007476:Ionophores; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; C037978:high density lipoprotein phosphatidylcholine; D008985:Monensin; D008049:Lipase; C495700:Lipc protein, mouse