Increased risk of cholesterol gallstone formation in subjects with apolipoprotein E4 genotype: Its relation to bile composition and crystalization

1998 ◽  
Vol 114 ◽  
pp. A547
Author(s):  
K.J. van Erpecum ◽  
P. Portincasa ◽  
E.R.M. Eckhardt ◽  
B.J.M. van de Heijning ◽  
A.K. Groen ◽  
...  
Keyword(s):  
Cholesterol Gallstone ◽  
Gallstone Formation ◽  
Bile Composition ◽  
Apolipoprotein E4 ◽  
Increased Risk

Increased risk of cholesterol gallstone formation in subjects with apolipoprotein E4 genotype

1998 ◽  
Vol 10 (12) ◽  
pp. A8
Author(s):  
K. J. van Erpecum ◽  
P. Portincasa ◽  
E. R.M. Eckhardt ◽  
B. J.M. van de Heijning ◽  
A. K. Groen ◽  
...  
Keyword(s):  
Cholesterol Gallstone ◽  
Gallstone Formation ◽  
Apolipoprotein E4 ◽  
Increased Risk

Altered bile composition during cholesterol gallstone formation: Cause or effect?

1990 ◽  
Vol 48 (6) ◽  
pp. 584-589 ◽  
Author(s):  
Thomas H. Magnuson ◽  
Keith D. Lillemoe ◽  
David E. Scheeres ◽  
Henry A. Pitt
Keyword(s):  
Cholesterol Gallstone ◽  
Gallstone Formation ◽  
Bile Composition

Inhibition of Ceramide Decreased the Expression of ATP-Binding Cassette Transporter G5/8 mRNA in an Animal Model of Cholesterol Gallstone

2017 ◽  
Vol 35 (5) ◽  
pp. 439-443 ◽  
Author(s):  
Hyo Jung Kim ◽  
Jae Seon Kim ◽  
Seikwan Oh ◽  
Hwan-Soo Yoo
Keyword(s):  
Cholesterol Gallstone ◽  
Specific Inhibitor ◽  
Gallstone Formation ◽  
Normal Group ◽  
Atp Binding ◽  
Chow Diet ◽  
Mrna Levels ◽  
Lithogenic Diet ◽  
Increased Risk ◽  
Atp Binding Cassette

Background: The increased risk of gallstone has been reported in patients with ATP-binding cassette (ABC) transporter polymorphism. The half-transporters ABCG5 and ABCG8 mediate the efflux of cholesterol in hepatocytes and the intestine. We investigated whether ceramide plays a role in cholesterol efflux through the ABC transporters. Methods: Six-week-old C57BL/6J mice were assigned to 3 groups. The normal group (n = 5) was fed a normal chow diet, the cholesterol group (n = 10) was fed a lithogenic diet, and the myriocin group (n = 15) was fed the lithogenic diet and myriocin, a specific inhibitor of serine-palmitoyl transferase. After 6 weeks, the ABCG5 and ABCG8 transporters were analyzed. Results: The rate of cholesterol gallstone formation in cholesterol group was also higher than that in normal and myriocin groups (0, 70, and 40%, respectively). ABCG5 and ABCG8 mRNA levels were significantly increased in cholesterol group and less increased in myriocin group, relative to that in normal group (p < 0.05). Conclusions: The inhibition of ceramide biosynthesis by myriocin suppressed gallstone formation and ABCG5/8 mRNA expression. We expect that ceramide's role as a regulator of the ABCG5/8 transporter might be linked to cholesterol gallstone formation.

scholarly journals Osteopontin Deficiency Alters Biliary Homeostasis and Protects against Gallstone Formation

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jing Lin ◽  
Ming Lu ◽  
Wei-qing Shao ◽  
Zong-you Chen ◽  
Wen-wei Zhu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cholesterol Gallstone ◽  
Gallstone Formation ◽  
Mechanistic Studies ◽  
Wild Type ◽  
Biliary Cholesterol ◽  
Cholesterol Crystals ◽  
Bile Composition ◽  
Hepatic Genes ◽  
Deficient Mice

Abstract The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in cholesterol gallstone formation is undetermined. In this study, we found that the expression of hepatic OPN was increased in gallstone patients compared with gallstone-free counterparts. Then, we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone formation than wild type mice. Further mechanistic studies revealed that this protective effect was associated with alterations of bile composition and was caused by the increased hepatic CYP7A1 expression and the reduced expression of hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the expression of hepatic OPN and the expression of these hepatic genes were validated in gallstone patients. Taken together, our findings reveal that hepatic OPN contributes to cholesterol gallstone formation by regulating biliary metabolism and might be developed as a therapeutic target for gallstone treatments.

scholarly journals T-Cell Function Is Critical for Murine Cholesterol Gallstone Formation

2007 ◽  
Vol 133 (4) ◽  
pp. 1304-1315 ◽  
Author(s):  
Kirk J. Maurer ◽  
Varada P. Rao ◽  
Zhongming Ge ◽  
Arlin B. Rogers ◽  
Trisha J. Oura ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Cholesterol Gallstone ◽  
Gallstone Formation ◽  
T Cell Function

scholarly journals Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice

2000 ◽  
Vol 4 (1) ◽  
pp. 59-65 ◽  
Author(s):  
BEVERLY PAIGEN ◽  
NICHOLAS J. SCHORK ◽  
KAREN L. SVENSON ◽  
YIN-CHAI CHEAH ◽  
JIAN-LONG MU ◽  
...  
Keyword(s):  
Quantitative Trait ◽  
Congenic Strain ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Gallstone Formation ◽  
Quantitative Trait Loci Mapping ◽  
Cholesterol Gallstones ◽  
Lithogenic Diet ◽  
The Difference ◽  
Trait Locus

Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR × C57L) F1× AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at ∼20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK.L- Lith1s. Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L- Lith2s. Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.

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