%0 Journal Article
%T Decreased NPC1L1 expression in the liver from Chinese female gallstone patients
%A Wei Cui
%A Zhao-Yan Jiang
%A Qu Cai
%A Ru-Yuan Zhang
%A Wei-Ze Wu
%A Jian-Cheng Wang
%A Jian Fei
%A Sheng-Dao Zhang
%A Tian-Quan Han
%J Lipids in Health and Disease
%D 2010
%I BioMed Central
%R 10.1186/1476-511x-9-17
%X The aim of this study is to probe for underlying hepatic molecular defects associated with development of gallstones in female.Fifty-seven nonobese, normolipidemic Chinese female gallstone patients (GS) were investigated with 12 age- and body mass index-matched female gallstone-free controls (GSF). The bile from the female GS had higher cholesterol saturation than that from the female GSF. The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels. Consistently, immunohistochemistry showed decreased NPC1L1 expression in female GS.The decreased hepatic NPC1L1 levels in female GS might indicate a downregulated reabsorption of biliary cholesterol in the liver, which, in turn, leads to the cholesterol supersaturation of bile. Our data are consistent with the possibility that hepatic NPC1L1 may be mediated by SREBP2.Cholesterol gallstone disease is common in both industrialized and developing countries [1,2]. Several clinical investigations have found an association between the increased incidence of cholesterol gallstones in China and a westernization of the traditional Chinese diet [2-4]. And because of the world-wide obesity epidemic with insulin resistance being part of the metabolic syndrome, the prevalence of cholesterol gallstones seems to be rising.As found by epidemiological and clinical studies, women are twice as likely as men to form cholesterol gallstones at all ages, and estrogen could be an important risk factor for the formation of cholesterol gallstones. A large number of human and animal studies have proposed that estrogen increases the risk of developing cholesterol gallstones by increasing the hepatic secretion of biliary cholesterol.Hypersecretion of biliary cholesterol and cholesterol supersaturation of the bile are considered to be the most important prerequisites for gallstone formation. Presently, the pathways for the biliary cholesterol secretion in the liver are inc
%U http://www.lipidworld.com/content/9/1/17