Identification of a nuclear receptor for bile acids
Abstract
Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.
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Both BAR and GPBAR1 can be activated by primary and secondary bile acids alike.
“Both receptors can be activated by primary and secondary bile acids alike (Kawamata et al., 2003; Makishima et al., 1999; Maruyama et al., 2002; Parks et al., 1999; H. Wang et al., 1999).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Makishima et al., 1999
Changes in the GM's composition correspond to changes in blood and brain BA profiles, and specific BA ligands' physicochemical properties determine the potency of BA receptor activation.
“Changes in the GM’s composition correspond to changes in blood and brain BA profiles, which are essential because specific BA ligands’ distinct physicochemical properties determine the potency of BA receptor activation (320–323).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [322]
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“Both receptors can be activated by primary and secondary bile acids alike (Kawamata et al., 2003; Makishima et al., 1999; Maruyama et al., 2002; Parks et al., 1999; Wang et al., 1999).”
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- Authors
- 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.
- Affiliations
- Howard Hughes Medical Institute (US)
- Tularik Incorporated, Two Corporate Drive, South San Francisco, CA 94080, USA.
- Corresponding author
- Makishima, Makoto
- Okamoto, Arthur Y.
- Repa, Joyce J.
- Mangelsdorf, David J.
- Venue
- Science
- Published
- 1999-05-21
- Volume
- 284
- Issue
- 5418
- Pages
- 1362-1365
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2053581007
- Cited by
- 2,714
- References
- 20
- Citations by year
- 2026: 96 · 2025: 82 · 2024: 100 · 2023: 100 · 2022: 143 · 2021: 127 · 2020: 127 · 2019: 134 · 2018: 113 · 2017: 133 · 2016: 94 · 2015: 110 · 2014: 88 · 2013: 93 · 2012: 107
- FWCI
- 35.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- bile acids, farnesoid X receptor, nuclear receptors, orphan receptors, CYP7A1, bile acid synthesis, enterohepatic circulation, transcriptional regulation, bile acid transport
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Biological Transport, Carrier Proteins, Cell Line, Chenodeoxycholic Acid, Cholesterol, Cholesterol 7-alpha-Hydroxylase, DNA-Binding Proteins, Gene Expression Regulation, Homeostasis, Humans, Hydroxysteroid Dehydrogenases, Ligands, Liver, Membrane Glycoproteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Receptors, Cytoplasmic and Nuclear, Symporters, Organic Anion Transporters, Sodium-Dependent, 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific), Mice, Histone Acetyltransferases, Nuclear Receptor Coactivator 1
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