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Cholic acid mediates negative feedback regulation of bile acid synthesis in mice
Abstract
Cholesterol is converted into dozens of primary and secondary bile acids through pathways subject to negative feedback regulation mediated by the nuclear receptor farnesoid X receptor (FXR) and other effectors. Disruption of the sterol 12α-hydroxylase gene (Cyp8b1) in mice prevents the synthesis of cholate, a primary bile acid, and its metabolites. Feedback regulation of the rate-limiting biosynthetic enzyme cholesterol 7α-hydroxylase (CYP7A1) is lost in Cyp8b1–/– mice, causing expansion of the bile acid pool and alterations in cholesterol metabolism. Expression of other FXR target genes is unaltered in these mice. Cholate restores CYP7A1 regulation in vivo and in vitro. The results implicate cholate as an important negative regulator of bile acid synthesis and provide preliminary evidence for ligand-specific gene activation by a nuclear receptor.
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“and Cyp8b1 KO (sgCyp8b1) decreased the levels of TCA, as expected (23).”
From Bile acid synthesis impedes tumor-specific T cell responses during liver cancer (2025) · cites this paper as [23]
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“This process is controlled by a negative-feedback loop through the activation of the nuclear farnesoid X receptor (FXR) in the ileum and liver (7, 8).”
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Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589
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: Natural Ligands for an Orphan Nuclear Receptor
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., et al. (1999) · Science · doi:10.1126/science.284.5418.1365 · Cited by 2,274
Nuclear Receptors and Lipid Physiology: Opening the X-Files
Chawla, A., Repa, J. J., Evans, R. M., & Mangelsdorf, D. J. (2001) · Science · doi:10.1126/science.294.5548.1866 · Cited by 2,085
A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis
Goodwin, B., Jones, S. A., Price, R. R., Watson, M. A., McKee, D. D., Moore, L. B., Galardi, C., Wilson, J. G., Lewis, M. C., Roth, M. E., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00051-4 · Cited by 1,940
Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G., & Gonzalez, F. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00062-3 · Cited by 1,819
Mansour, S. L., Thomas, K. R., & Capecchi, M. R. (1988) · Nature · doi:10.1038/336348a0 · Cited by 1,683
Endogenous Bile Acids Are Ligands for the Nuclear Receptor FXR/BAR
Wang, H., Chen, J., Hollister, K., Sowers, L. C., & Forman, B. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80348-2 · Cited by 1,636
An oxysterol signalling pathway mediated by the nuclear receptor LXRα
Janowski, B. A., Willy, P. J., Devi, T. R., Falck, J. R., & Mangelsdorf, D. J. (1996) · Nature · doi:10.1038/383728a0 · Cited by 1,591
An Orphan Nuclear Receptor Activated by Pregnanes Defines a Novel Steroid Signaling Pathway
Kliewer, S. A., Moore, J. T., Wade, L., Staudinger, J. L., Watson, M. A., Jones, S. A., McKee, D. D., Oliver, B. B., Willson, T. M., Zetterström, R. H., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80900-9 · Cited by 1,534
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Németh, K., Kiss, D. S., Lányi, K., Csorba, S., Bartha, T., Pápa, K., & Sterczer, Á. (2026) · Food Hydrocolloids for Health · doi:10.1016/j.fhfh.2026.100275 · Cited by 3
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Tacer, K. F. (2020) · Springer eBooks · doi:10.1007/978-3-030-39684-8_6 · Cited by 3
Zhao, A., Wang, X. D., Chen, G. H., & Lu, L. (2011) · Poultry Science · doi:10.3382/ps.2010-01207 · Cited by 2
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John, C., Werner, P., Heeren, J., & Fischer, M. J. (2017) · doi:10.1002/9781119413073.ch20 · Cited by 2
Du, X. Y., Xu, X., Niu, D., Tian, Y., Tao, Z., Cai, Z., & Lu, L. (2020) · Journal of Applied Animal Research · doi:10.1080/09712119.2020.1764848 · Cited by 1
Tanaka, Y., Inaba, C., Sawa, T., Endo, K., Saiki, T., Haga, H., & Tanaka, S. (2023) · Bioscience Biotechnology and Biochemistry · doi:10.1093/bbb/zbad086 · Cited by 1
Heida, A., van Dijk, T. H., Smit, M., Koehorst, M., Koster, M. H., Kloosterhuis, N., Havinga, R., Bloks, V. W., Wolters, J. C., de Bruin, A., et al. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2023.159445 · Cited by 1
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In vitro evidence of possible influence of scutellarein towards bile acids’ metabolism
Shu-Yao, Z., Hong, J., Chao-xian, L., Zhi-Wei, Z., Xin, D., & Lei, C. (2013) · African Health Sciences · doi:10.4314/ahs.v13i3.4 · Cited by 1
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D'Amico, A. V., & Stanford, J. S. (2009) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2008.0337 · Cited by 1
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Xu, G., & Salen, G. (2009) · doi:10.1002/9780470747919.ch22 · Cited by 1
Nawae, W., Sonthirod, C., Yoocha, T., Waiyamitra, P., Soisook, P., Tangphatsornruang, S., & Pootakham, W. (2022) · DNA Research · doi:10.1093/dnares/dsac026
Mechanism of metabolic surgery for the treatment of Type 2 Diabetes Mellitus (T2DM)
Leishman, D. J., Ikramuddin, S., & Naitoh, T. (2023) · Mini-invasive Surgery · doi:10.20517/2574-1225.2023.29
Liu, H., Tian, R., Wang, H., Feng, S., Li, H., Xiao, Y., Luan, X., Zhang, Z., Shi, N., Niu, H., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13076628
Ferraz, Á. A. B., Vianna, C. D. B., Henriques, D., Gorgulho, G. C. F., Santa‐Cruz, F., Siqueira, L. T., & Kreimer, F. (2024) · Surgical Laparoscopy Endoscopy & Percutaneous Techniques · doi:10.1097/sle.0000000000001348
Lay, A. L., Brial, F., Rouch, C., Shao, X., Bourgey, M., Sonomura, K., Ou, H., Ghezzal, S., Vincent, M., Rugard, M., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-29273-y
Bansal, M., Fu, Y., Alrubaye, B., Abraha, M., Almansour, A. M., Gupta, A., Liyanage, R., Wang, H., Hargis, B., & Sun, X. (2020) · Figshare · doi:10.6084/m9.figshare.11979633
Liu, H., Tian, R., Wang, H., Feng, S., Li, H., Xiao, Y., Luan, X., Zhang, Z., Shi, N., Niu, H., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13076631
Wang, Y., Zhao, J., Li, Q., Liu, J., Sun, Y., Zhang, K., MingCong, F., Qian, H., Li, Y., & Wang, L. (2022) · Figshare · doi:10.6084/m9.figshare.19607701
Chen, M., Cao, J., Fu, S., Han, Y., Chen, J., Yang, X. H., & Wang, J. (2026) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2026.105991
McCracken, A. B., Li, D., Caldwell, J. P., Lankin, C., Tagat, J. R., Khan, T., Rao, A., Zhang, T., Caplen, M. A., Verras, A., et al. (2026) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6c00387
BindingDB Entry 50020665: Aminopyrrolidineamide inhibitors of site-1 protease.
BindingDB (2009) · UC San Diego · doi:10.7270/q26m36jg
Metadata
- Authors
- Li-Hawkins, J., Gåfvels, M., Olin, M., Lund, E. G., Andersson, U., Schuster, G., Björkhem, I., Russell, D. W., & Eggertsen, G.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Karolinska Institutet (SE)
- Corresponding author
- Russell, David W.
- Venue
- Journal of Clinical Investigation
- Published
- 2002-10-15
- Volume
- 110
- Issue
- 8
- Pages
- 1191-1200
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4239553605
- Cited by
- 227
- References
- 45
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 13 · 2023: 13 · 2022: 11 · 2021: 16 · 2020: 21 · 2019: 12 · 2018: 16 · 2017: 7 · 2016: 12 · 2015: 6 · 2014: 8 · 2013: 7 · 2012: 9
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Funders
- W. M. Keck Foundation
- National Institutes of Health (HL20948)
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- cholic acid, cholate, bile acid synthesis, negative feedback regulation, farnesoid X receptor, CYP8B1, sterol 12alpha-hydroxylase, CYP7A1, cholesterol metabolism
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