Biliary lipids, water and cholesterol gallstones

  • van Erpecum K
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Abstract

Cholesterol supersaturation, hydrophobic bile salts, pronucleating proteins and impaired gall‐bladder motility may contribute to gallstone pathogenesis. We here show that both gallstone‐susceptible C57L and gallstone‐resistant AKR male inbred mice exhibit supersaturated gall‐bladder biles during early lithogenesis, whereas bile‐salt composition becomes hydrophobic only in susceptible C57L mice. In vitro , cholesterol crystallization occurs depending on relative amounts of lipids; excess cholesterol may exceed solubilizing capacity of mixed bile salt—phospholipid micelles, whereas excess bile salts compared with phospholipids leads to deficient cholesterol‐storage capacity in vesicles. In vivo , bile lipid contents are mainly determined at the level of the hepatocyte canalicular membrane, where specific transport proteins enable lipid secretion [ABCG5/G8 (ATP‐binding cassette transporter G5/G8) for cholesterol, MDR3 (multi‐drug resistant 3) for phospholipid, BSEP (bile salt export pump)]. These transport proteins are regulated by farnesoid X and liver X nuclear receptors. After nascent bile formation, modulation of bile water contents in biliary tract and gall‐bladder exerts critical effects on cholesterol crystallization. During progressive bile concentration (particularly in the fasting gall‐bladder), cholesterol and, preferentially, phospholipid transfer occurs from cholesterol‐unsaturated vesicles to emerging mixed micelles. The remaining unstable cholesterol‐enriched vesicles may nucleate crystals. Various aquaporins have recently been discovered throughout the biliary tract, with potential relevance for gallstone formation.

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APA

van Erpecum, K. J. (2005). Biliary lipids, water and cholesterol gallstones. Biology of the Cell, 97(11), 815–822. https://doi.org/10.1042/bc20040088

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