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

Abstract

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 chowfed 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.

Les protéines à domaine START, des trafiquants intracellulaires de lipides

“…-/-ont des difficultés à éliminer les excès de PC, d'acides biliaires et de cholestérol par la bile [21], suggérant l'implication physiologique de cette protéine dans le métabolisme des phospholipides. Rappelons que STARD2, STARD7 et STARD10 sont co-exprimées dans le foie, et ces deux dernières pourraient compenser l'absence de STARD2 chez les souris STARD2 -/- [20].…”

A polymorphism in New Zealand inbred mouse strains that inactivates phosphatidylcholine transfer protein

“…Indeed, this region was found to contain Pctp, the gene encoding phosphatidylcholine transfer protein (PC-TP). PC-TP is a highly specific 25 kDa PC binding protein that is enriched in cytosol of hepatocytes [5,6] and regulates lipid metabolism in the liver [7][8][9]. In the present report, we show that the NZO genome carries a functionally null Pctp allele, which was present only in two other closely related New Zealand mouse strains.…”

“…It is expressed in a number of human [24] and mouse [23] tissues, but highest levels are generally found in the liver. Experiments in tissue culture [25,26] and in mice with homozygous disruption of Pctp [7][8][9] suggest a role for PC-TP in hepatobiliary elimination of plasma cholesterol.…”

“…Egg yolk PC, brain phosphatidylserine (PS) and bovine heart cardiolipin were from Avanti Polar Lipids (Alabaster, AL). L L-a-1-Palmitoyl-2-linoleoyl-[linoleoyl- [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C] PC (50 mCi/mmol) was from NEN Life Science Products (Boston, MA) and [1a,a(n)- 3 H] and cholesteryl oleate (44 Ci/mmol) was from Amersham Biosciences (GE Healthcare Bio-Sciences Corp., Piscataway, NJ).…”

Diet-induced lipid accumulation in phospholipid transfer protein-deficient mice: its atherogenicity and potential mechanism

“…Furthermore, phosphatidylcholine transfer protein (PC-TP), another protein which mediates transfer of phosphatidylcholine, has been implicated in biliary lipid secretion. Pc-tp -defi cient mice have impaired biliary lipid secretion when fed a high-fat, high-cholesterol diet but not when fed a chow diet ( 44 ). Although PLTP is generally thought to function in the circulation, there is evidence for an intracellular role of PLTP ( 4,45 ).…”