Prevention of cholesterol gallstone disease by FXR agonists in a mouse model

Antonio Moschetta, Angie L. Bookout, David J. Mangelsdorf

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1352-1358
Number of pages7
JournalNature Medicine
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2004

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Gallstones
Cholesterol
Bile Acids and Salts
Cholecystitis
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Bile
Solubility
Phospholipids
Phenotype

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Moschetta, A., Bookout, A. L., & Mangelsdorf, D. J. (2004). Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nature Medicine, 10(12), 1352-1358. https://doi.org/10.1038/nm1138

Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. / Moschetta, Antonio; Bookout, Angie L.; Mangelsdorf, David J.

In: Nature Medicine, Vol. 10, No. 12, 12.2004, p. 1352-1358.

Research output: Contribution to journalArticle

Moschetta, A, Bookout, AL & Mangelsdorf, DJ 2004, 'Prevention of cholesterol gallstone disease by FXR agonists in a mouse model', Nature Medicine, vol. 10, no. 12, pp. 1352-1358. https://doi.org/10.1038/nm1138
Moschetta, Antonio ; Bookout, Angie L. ; Mangelsdorf, David J. / Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. In: Nature Medicine. 2004 ; Vol. 10, No. 12. pp. 1352-1358.
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