Increased expression of LXRα, 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 a (LXRa) 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 LXRa, 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

ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis

“…Eight studies were excluded, due to the inclusion of children ( 21 ), FH patients ( 22 ), subjects treated with cholesterollowering medication ( 6,23 ), unavailable cholesterol data ( 10,24,25 ), or a duplicate report ( 26 ).…”

HNF1α and SREBP2 are important regulators of NPC1L1 in human liver

“…As we recently reported ( 18 ), no signifi cant differences were observed in NPC1L1, SREBP2, and HNF1 ␣ mRNA expression between GS and GSF patients, though GS patients had 43% ( P < 0.05) higher HNF4 ␣ mRNA expression compared with GSF patients.…”

Hepatic Niemann–Pick C1-like 1

“…Thus, low hepatic NPC1L1 expression would contribute to the formation of cholesterol gallstones by insufficient reabsorption of biliary cholesterol. We investigated this possibility in liver biopsies from a small cohort of normolipidemic and nonobese female and male Chinese patients and did not find any difference in the NPC1L1 mRNA expression between gallstone and gallstone-free patients [46]. However, when similar studies were performed in a larger group of gallstone patients, hepatic expression of NPC1L1 was reduced, but only in women [47].…”

“…However, of note is that the expression of scavenger receptor class B type I (SRBI) regulates plasma HDL levels and the biliary cholesterol secretion in mice [55,56]. Accordingly, hepatic expression of SRBI correlates with biliary cholesterol levels in humans [46]. Hence, it seems unlikely that biliary sterol excretion does not play a relevant role in RCT.…”