First Author | Wu MK | Year | 2005 |
Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 289 |
Issue | 6 | Pages | G1067-74 |
PubMed ID | 16099870 | Mgi Jnum | J:104778 |
Mgi Id | MGI:3612772 | Doi | 10.1152/ajpgi.00194.2005 |
Citation | Wu MK, et al. (2005) Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins. Am J Physiol Gastrointest Liver Physiol 289(6):G1067-74 |
abstractText | 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. |