Hepatic uptake and metabolism of phosphatidylcholine associated with high density lipoproteins |
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Authors: | Julie C. Robichaud Jelske N. van der Veen Zemin Yao Bernardo Trigatti Dennis E. Vance |
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Affiliation: | 1. Group on the Molecular and Cell Biology of Lipids and the Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2;2. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5;3. Atherothrombosis Research Group and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 |
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Abstract: | BackgroundPhosphatidylcholine (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.Methods and resultsThe absence of scavenger receptor-BI resulted in a 30% decrease in cellular incorporation of [3H]PC whereas [3H]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 A2 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 triacylglcyerol. The formation of triacylglcerol is independent of scavenger receptor-BI and occurs in extralysosomal compartments.Conclusions and general significanceThese 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. |
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Keywords: | ATK, arachidonyl trifluoromethyl ketone CE, cholesteryl ester CEt, cholesteryl ether CETP, cholesterol ester transfer protein DGAT, diacylglycerol acyltransferase DMEM, Dulbecco's modified Eagle's medium HDL, high density lipoprotein HL, hepatic lipase LCAT, lecithin:cholesterol acyltransferase LDL, low density lipoprotein LDLr, low density lipoprotein receptor LPL, lipoprotein lipase PBS, phosphate buffered saline PC, phosphatidylcholine PLA2, phospholipase A2 PLC, phospholipase C SR-BI, scavenger receptor class B type I TG, triacylglycerol |
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