title: Increased expression of LXR alpha, ABCG5, ABCG8, and SR-BI in the liver from normolipidemic, nonobese Chinese gallstone patients.
abstract: Cholesterol supersaturation of bile is one prerequisite for gallstone formation. In the present study of Chinese patients with gallstones, we investigated whether this phenomenon was correlated with the hepatic expression of genes participating in the metabolism of cholesterol and bile acids. Twenty-two nonobese, normolipidemic patients (female-male, 11:11) with gallstones were investigated with 13 age- and body mass index-matched gallstone-free controls (female-male, 10:3). The bile from the gallstone patients had higher cholesterol saturation than that from the controls. The mRNA levels of ABCG5, ABCG8, and liver X receptor alpha (LXRalpha) in the gallstone patients were increased by 51, 59, and 102%, respectively, and significantly correlated with the molar percentage of biliary cholesterol and cholesterol saturation index (CSI). The mRNA and protein levels of the hepatic scavenger receptor class B type I (SR-BI) were increased, and a significant correlation was found between the protein levels and the CSI. No differences were recorded between the two groups concerning the hepatic synthesis of cholesterol, bile acids, and esterification of cholesterol. Our results suggest that the upregulation of ABCG5/ABCG8 in gallstone patients, possibly mediated by increased LXRalpha, may contribute to the cholesterol supersaturation of bile. Our data are consistent with the possibility that increased amounts of biliary cholesterol may originate from plasma HDL cholesterol by enhanced transfer via SR-BI.
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Surgery, 200025 Shanghai, China.
authors.forename: Zhao-Yan
authors.initials: ZY
authors.lastname: Jiang
authors.forename: Paolo
authors.initials: P
authors.lastname: Parini
authors.forename: Gösta
authors.initials: G
authors.lastname: Eggertsen
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Davis
authors.forename: Hai
authors.initials: H
authors.lastname: Hu
authors.forename: Guang-Jun
authors.initials: GJ
authors.lastname: Suo
authors.forename: Sheng-Dao
authors.initials: SD
authors.lastname: Zhang
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Rudel
authors.forename: Tian-Quan
authors.initials: TQ
authors.lastname: Han
authors.forename: Curt
authors.initials: C
authors.lastname: Einarsson
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism; D002681:China; D002769:Cholelithiasis / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D005260:Female; D042882:Gallstones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D004268:DNA-Binding Proteins; D008055:Lipids; D008074:Lipoproteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B