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Is the FXR the fix for cholesterol gallstone disease?
Author(s) -
Juran Brian D.,
Lazaridis Konstantinos N.
Publication year - 2005
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20776
Subject(s) - farnesoid x receptor , cholesterol , medicine , bile acid , reverse cholesterol transport , gallbladder , agonist , disease , taurocholic acid , endocrinology , receptor , chemistry , nuclear receptor , biochemistry , lipoprotein , transcription factor , gene
Cholesterol gallstone disease is characterized by several events, including cholesterol precipitation in bile, increased bile salt hydrophobicity and gallbladder inflammation. Here, we describe the same phenotype in mice lacking the bile acid receptor, FXR. Furthermore, in susceptible wild‐type mice that recapitulate human cholesterol gallstone disease, treatment with a synthetic FXR agonist prevented sequelae of the disease. These effects were mediated by FXR‐dependent increases in biliary bile salt and phospholipid concentrations, which restored cholesterol solubility and thereby prevented gallstone formation. Taken together, these results indicate that FXR is a promising therapeutic target for treating or preventing cholesterol gallstone disease.