Decreased NPC1L1 expression in the liver from Chinese female gallstone patients.
BACKGROUND
Cholesterol gallstone disease is a very common disease in both industrialized and developing countries. Many studies have found that cholesterol gallstones are more common in women than men. The molecular mechanisms underlying the relationship between female gallstone disease and hepatic sterol transporters are still undergoing definition and have not been evaluated in humans.


OBJECTIVE
The aim of this study is to probe for underlying hepatic molecular defects associated with development of gallstones in female.


RESULTS
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.


CONCLUSIONS
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.
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Surgery, 200025, Shanghai, PR China.
Wei
W
Cui
Zhao-Yan
ZY
Jiang
Qu
Q
Cai
Ru-Yuan
RY
Zhang
Wei-Ze
WZ
Wu
Jian-Cheng
JC
Wang
Jian
J
Fei
Sheng-Dao
SD
Zhang
Tian-Quan
TQ
Han
D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D042882:Gallstones / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000096:biosynthesis; D013261:Sterols / Q000737:chemistry
D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D012333:RNA, Messenger; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D013261:Sterols; D002784:Cholesterol