Cited by 1,819Drug Transport and Resistance MechanismsCholesterol and Lipid MetabolismLipid metabolism and disorders

Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis

Open access
Sinal, Christopher J, Tohkin, Masahiro, Miyata, Masaaki, Ward, Jerrold M, Lambert, Gilles, Gonzalez, Frank J·2000·Cell

Abstract

Mice lacking the nuclear bile acid receptor FXR/BAR developed normally and were outwardly identical to wild-type littermates. FXR/BAR null mice were distinguished from wild-type mice by elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. FXR/BAR null mice also had reduced bile acid pools and reduced fecal bile acid excretion due to decreased expression of the major hepatic canalicular bile acid transport protein. Bile acid repression and induction of cholesterol 7alpha-hydroxylase and the ileal bile acid binding protein, respectively, did not occur in FXR/BAR null mice, establishing the regulatory role of FXR/BAR for the expression of these genes in vivo. These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor.

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Crossref · 10.1016/s0092-8674(00)00062-3

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Authors
Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G., & Gonzalez, F. J.
Affiliations
National Institutes of Health (US)
Corresponding author
Gonzalez, Frank J
Venue
Cell
Publisher
Elsevier BV
Published
2000-09
Volume
102
Issue
6
Pages
731-744
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2051040521
Cited by
1,819
References
76
Citations by year
2026: 46 · 2025: 63 · 2024: 75 · 2023: 83 · 2022: 89 · 2021: 83 · 2020: 81 · 2019: 77 · 2018: 79 · 2017: 83 · 2016: 69 · 2015: 61 · 2014: 68 · 2013: 69 · 2012: 74
FWCI
27.89
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
farnesoid X receptor, bile acid homeostasis, lipid homeostasis, CYP7A1, ileal bile acid binding protein, bile acid transport, fecal bile acid excretion, liver cholesterol, serum lipoproteins, atherosclerosis, knockout mice
MeSH terms
Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Biological Transport, Cholesterol 7-alpha-Hydroxylase, Cholesterol, Dietary, DNA-Binding Proteins, Female, Homeostasis, Liver, Male, RNA, Messenger, Transcription Factors, Triglycerides, Gene Expression, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Mice

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