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Bile Acids: Natural Ligands for an Orphan Nuclear Receptor
Abstract
Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.
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“However, in the presence of CDCA, which is present under physiological conditions, DCA and LCA appear to be antagonists of the FXR receptor (Parks et al., 1999; Yu et al., 2002).”
From Akkermansia muciniphila alleviates high‐fat‐diet ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Parks et al., 1999
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Sorted by citations
Identification of a nuclear receptor for bile acids
Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., Hull, M. V., Lustig, K. D., Mangelsdorf, D. J., & Shan, B. (1999) · Science · doi:10.1126/science.284.5418.1362 · Cited by 2,714
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
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Russell, D. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161712 · Cited by 2,069
Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis
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A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis
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Self-citation
Metadata
- Authors
- Parks, D. J., Blanchard, S. G., Bledsoe, R. K., Chandra, G., Consler, T. G., Kliewer, S. A., Stimmel, J. B., Willson, T. M., Zavacki, A. M., Moore, D. D., & Lehmann, J. M.
- Affiliations
- Molecular Biochemistry,
- Molecular Sciences,
- Molecular Endocrinology,
- Medicinal Chemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA.
- Baylor College of Medicine (US)
- Corresponding author
- Willson, Timothy M.
- Venue
- Science
- Published
- 1999-05-21
- Volume
- 284
- Issue
- 5418
- Pages
- 1365-1368
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2171398834
- Cited by
- 2,274
- References
- 3
- Citations by year
- 2026: 66 · 2025: 72 · 2024: 86 · 2023: 75 · 2022: 103 · 2021: 111 · 2020: 102 · 2019: 105 · 2018: 101 · 2017: 113 · 2016: 80 · 2015: 90 · 2014: 80 · 2013: 83 · 2012: 93
- FWCI
- 78.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5f32dk009793-02)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053366, R01-DK53366, F32 DK09793)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- bile acids, farnesoid X receptor, orphan nuclear receptor, cholesterol homeostasis, chenodeoxycholic acid, lithocholic acid, deoxycholic acid, bile acid conjugates, SRC-1, transcriptional regulation
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Carrier Proteins, Cell Line, Chenodeoxycholic Acid, Cholesterol, Deoxycholic Acid, DNA-Binding Proteins, Homeostasis, Humans, Ligands, Lithocholic Acid, Protein Conformation, Recombinant Fusion Proteins, Structure-Activity Relationship, Transcription Factors, Transfection, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Symporters, Organic Anion Transporters, Sodium-Dependent, Mice, Histone Acetyltransferases, Nuclear Receptor Coactivator 1
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