title: Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Department of Medicine I and the Department of Medicine II, University Hospital of Lübeck, Lübeck, Germany. fuchs@medinf.mu-luebeck.de
authors.forename: M
authors.initials: M
authors.lastname: Fuchs
authors.forename: B
authors.initials: B
authors.lastname: Ivandic
authors.forename: O
authors.initials: O
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Schalla
authors.forename: J
authors.initials: J
authors.lastname: Scheibner
authors.forename: P
authors.initials: P
authors.lastname: Bartsch
authors.forename: E F
authors.initials: EF
authors.lastname: Stange
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002769:Cholelithiasis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D004032:Diet; D004798:Enzymes / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008806:Mice, Inbred AKR / Q000502:physiology; D008815:Mice, Inbred Strains / Q000235:genetics; D016601:RNA-Binding Proteins; D011973:Receptors, LDL / Q000235:genetics; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D004798:Enzymes; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D016601:RNA-Binding Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D002784:Cholesterol