J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700295-JLR200 on November 15, 2007

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Journal of Lipid Research, Vol. 49, 464-472, February 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology


Patient-Oriented and Epidemiological Research

Increased expression of LXR{alpha}, ABCG5, ABCG8, and SR-BI in the liver from normolipidemic, nonobese Chinese gallstone patients

Zhao-Yan Jiang1,*,{dagger},§, Paolo Parini1,§,**, Gösta Eggertsen§, Matthew A. Davis{dagger}{dagger}, Hai Hu§§, Guang-Jun Suo§§, Sheng-Dao Zhang*, Lawrence L. Rudel{dagger}{dagger}, Tian-Quan Han2,* and Curt Einarsson2,{dagger}

* Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Surgery, 200025 Shanghai, China
{dagger} Division of Hepatology and Gastroenterology, Department of Medicine, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden
§ Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden
** Molecular Nutrition Unit, Center for Nutrition and Toxicology, Department of Bioscience and Nutrition, NOVUM, Karolinska Institutet at Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden
{dagger}{dagger} Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157
§§ Department of Surgery, Shanghai Oriental Hospital, 200120 Shanghai, China

Published, JLR Papers in Press, November 15, 2007.

1 Z-Y Jiang and P. Parini contributed equally to this study.

2 To whom correspondence should be addressed. e-mail: digsurgrj{at}yahoo.com.cn (T-Q.H.); curt.einarsson{at}ki.se (C.E.)

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} (LXR{alpha}) 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 LXR{alpha}, 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.

Supplementary key words scavenger receptor class B type I • hepatocyte nuclear factor 4{alpha} • acyl-coenzyme A:cholesterol acyltransferase 2 • nuclear receptors • ATP binding cassette G5 • ATP binding cassette G8 • bile acids • cholesteryl esters • liver X receptor {alpha}

Abbreviations: apoA-I, apolipoprotein A-I; CSI, cholesterol saturation index; CYP7A1, cholesterol 7{alpha}-hydroxylase; FXR, farnesoid X receptor; GS, gallstone patients; GSF, gallstone-free controls; HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; HNF4A, hepatocyte nuclear factor 4{alpha}; LXR{alpha}, liver X receptor {alpha}; MTTP, microsomal triglyceride transfer protein; PGC1{alpha}, peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha}; SR-BI, scavenger receptor class B type I; SREBP, sterol-regulatory element binding protein


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