Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI

Hepatology. 2001 Jun;33(6):1451-9. doi: 10.1053/jhep.2001.24373.


Enhanced hepatocellular trafficking of cholesterol to the bile canaliculus and cholesterol hypersecretion appears critical for gallstone formation. Therefore, we studied in more detail the hepatic cholesterol transport pathways in a mouse model of cholesterol gallstone disease. Biliary lipid secretion rates, plasma lipoprotein levels, hepatic expression of lipoprotein receptors, lipid regulatory enzymes, and putative cholesterol transporting proteins were analyzed in gallstone-susceptible C57L/J and gallstone-resistant AKR/J mice, which were fed a lithogenic diet. Biliary cholesterol hypersecretion in C57L mice was associated with decreased plasma high-density lipoprotein (HDL) cholesterol levels and significant hepatic induction of the HDL receptor (SRBI) and cholesteryl ester hydrolase. In response to the lithogenic diet, fatty-acid binding protein of liver (FABPL) was markedly induced in both mouse strains. Caveolin 1 was elevated only in plasma membranes of gallstone-susceptible C57L mice, which also failed to down-regulate cholesterol synthesis. These data suggest a role of the reverse cholesterol transport pathway for genetically determined gallstone susceptibility in the mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism*
  • Carrier Proteins / metabolism
  • Cholelithiasis / etiology
  • Cholelithiasis / genetics*
  • Cholelithiasis / metabolism*
  • Cholelithiasis / pathology
  • Cholesterol / metabolism*
  • Diet
  • Enzymes / metabolism
  • Enzymes / physiology
  • Gene Expression
  • Genetic Predisposition to Disease*
  • Immunity, Innate
  • Lipid Metabolism
  • Lipoproteins / blood
  • Lipoproteins, HDL*
  • Liver / metabolism*
  • Liver / pathology
  • Mice
  • Mice, Inbred AKR / physiology
  • Mice, Inbred Strains / genetics
  • RNA-Binding Proteins*
  • Receptors, LDL / genetics
  • Receptors, Lipoprotein / genetics
  • Receptors, Lipoprotein / metabolism*
  • Up-Regulation


  • Carrier Proteins
  • Enzymes
  • Lipoproteins
  • Lipoproteins, HDL
  • RNA-Binding Proteins
  • Receptors, LDL
  • Receptors, Lipoprotein
  • high density lipoprotein receptors
  • high density lipoprotein binding protein
  • Cholesterol