J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M400387-JLR200 on December 1, 2004

Papers In Press, published online ahead of print March 1, 2005
J. Lipid Res., doi:10.1194/jlr.M400387-JLR200
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Journal of Lipid Research, Vol. 46, 422-431, March 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Impaired response of biliary lipid secretion to a lithogenic diet in phosphatidylcholine transfer protein-deficient mice

Michele K. Wu*, Hideyuki Hyogo{dagger}, Suresh K. Yadav{dagger}, Phyllis M. Novikoff§ and David E. Cohen1,*,{dagger}

* Departments of Biochemistry, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461
{dagger} Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461
§ Pathology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461

1 To whom correspondence should be addressed. e-mail: dcohen{at}partners.org

Phosphatidylcholine transfer protein (PC-TP) is a cytosolic lipid transfer protein that is highly expressed in liver and catalyzes intermembrane transfer of phosphatidylcholines in vitro. To explore a role for PC-TP in the hepatocellular trafficking of biliary phosphatidylcholines, we characterized biliary lipid secretion using Pctp–/– and wild-type littermate control mice with C57BL/6J and FVB/NJ genetic backgrounds, which express PC-TP at relatively high and low levels in liver, respectively. Eight-week-old male Pctp–/– and wild-type mice were fed a chow diet or a lithogenic diet, which served to upregulate biliary lipid secretion. In chow-fed mice, the absence of PC-TP did not reduce biliary phospholipid secretion or alter the phospholipid composition of biles. However, the responses in secretion of biliary phospholipids, cholesterol, and bile salts to the lithogenic diet were impaired in Pctp–/– mice from both genetic backgrounds. Alterations in biliary lipid secretion could not be attributed to transcriptional regulation of the expression of canalicular membrane lipid transporters, but possibly to a defect in their trafficking to the canalicular membrane.

These findings support a role for PC-TP in the response of biliary lipid secretion to a lithogenic diet, but not specifically in the hepatocellular transport and secretion of phosphatidylcholines.

Abbreviations: Abc, ATP binding cassette protein; PC-TP, phosphatidylcholine transfer protein; START, steroidogenic acute regulatory-related transfer; TC, taurocholate; TCDC, taurochenodeoxycholate; TDC, taurodeoxycholate; TMC, tauromuricholate; TUDC, tauroursodeoxycholate

Supplementary key words cholesterol • phospholipid • bile salt • bile • liver • gallstone • lipid transfer protein • bile canaliculi


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