Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins.
Phosphatidylcholine transfer protein (PC-TP) is a steroidogenic acute regulatory-related transfer domain protein that is enriched in liver cytosol and binds phosphatidylcholines with high specificity. In tissue culture systems, PC-TP promotes ATP-binding cassette protein A1-mediated efflux of cholesterol and phosphatidylcholine molecules as nascent pre-beta-high-density lipoprotein (HDL) particles. Here, we explored a role for PC-TP in HDL metabolism in vivo utilizing 8-wk-old male Pctp(-/-) and wild-type littermate C57BL/6J mice that were fed for 7 days with either chow or a high-fat/high-cholesterol diet. In chow-fed mice, neither plasma cholesterol concentrations nor the concentrations and compositions of plasma phospholipids were influenced by PC-TP expression. However, in Pctp(-/-) mice, there was an accumulation of small alpha-migrating HDL particles. This occurred without changes in hepatic expression of ATP-binding cassette protein A1 or in proteins that regulate the intravascular metabolism and clearance of HDL particles. In Pctp(-/-) mice fed the high-fat/high-cholesterol diet, HDL particle sizes were normalized, whereas plasma cholesterol and phospholipid concentrations were increased compared with wild-type mice. In the absence of upregulation of hepatic ATP-binding cassette protein A1, reduced HDL uptake from plasma into livers of Pctp(-/-) mice contributed to higher plasma lipid concentrations. These data indicate that PC-TP is not essential for the enrichment of HDL with phosphatidylcholines but that it does modulate particle size and rates of hepatic clearance.
Wu
Michele K
MK
Dept. of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA.
Cohen
David E
DE
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004591:Electrophoresis, Polyacrylamide Gel; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D049294:Phospholipid Transfer Proteins / Q000172:deficiency / Q000502:physiology*; D010743:Phospholipids / Q000097:blood; D014280:Triglycerides / Q000097:blood
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol