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Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Open accessAbstract
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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“FXR is required for the negative-feedback regulation of BA biosynthesis and the enterohepatic cycle (30).”
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Metadata
- 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
- ORCID
- 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
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › 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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