The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
In the citing paper
“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).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Molecular Basis for Feedback Regulation of Bile Acid Synthesis by Nuclear Receptors
Lu, T. T., Makishima, M., Repa, J. J., Schoonjans, K., Kerr, T. A., Auwerx, J., & Mangelsdorf, D. J. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00050-2 · Cited by 1,487
Peet, D. J., Turley, S. D., Ma, W., Janowski, B. A., Lobaccaro, J. A., Hammer, R. E., & Mangelsdorf, D. J. (1998) · Cell · doi:10.1016/s0092-8674(00)81432-4 · Cited by 1,428
Activation of the Nuclear Receptor LXR by Oxysterols Defines a New Hormone Response Pathway
Lehmann, J. M., Kliewer, S. A., Moore, L. B., Smith-Oliver, T. A., Oliver, B. B., Su, J.-L., Sundseth, S. S., Winegar, D. A., Blanchard, D. E., Spencer, T. A., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3137 · Cited by 1,233
Identification of a nuclear receptor that is activated by farnesol metabolites
Forman, B. M., Goode, E., Chen, J., Oro, A. E., Bradley, D. J., Perlmann, T., Noonan, D. J., Burka, L. T., McMorris, T., Lamph, W. W., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90530-8 · Cited by 1,210
Hayhurst, G. P., Lee, Y.-H., Lambert, G., Ward, J. M., & Gonzalez, F. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.4.1393-1403.2001 · Cited by 1,107
Russell, D. W., & Setchell, K. D. R. (1992) · Biochemistry · doi:10.1021/bi00135a001 · Cited by 819
Self-citationAnanthanarayanan, M., Balasubramanian, N., Makishima, M., Mangelsdorf, D. J., & Suchy, F. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011610200 · Cited by 804
Brodie, S. E. (1996) · Survey of Ophthalmology · doi:10.1016/s0039-6257(96)80075-0 · Cited by 770
Humanized xenobiotic response in mice expressing nuclear receptor SXR
Xie, W., Barwick, J. L., Downes, M., Blumberg, B., Simon, C. M., Nelson, M. C., Neuschwander‐Tetri, B. A., Brunt, E. M., Guzelian, P. S., & Evans, R. M. (2000) · Nature · doi:10.1038/35019116 · Cited by 661
Steroid 5α-reductase 2 deficiency
Mendonca, B. B., Batista, R. L., Domenice, S., Costa, E. M. F., Arnhold, I. J. P., Russell, D. W., & Wilson, J. D. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.05.020 · Cited by 545
Self-citationIdentification of a Chemical Tool for the Orphan Nuclear Receptor FXR
Maloney, P., Parks, D. J., Haffner, C. D., Fivush, A. M., Chandra, G., Plunket, K. D., Creech, K. L., Moore, L. B., Wilson, J. G., Lewis, M. C., et al. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm0002127 · Cited by 536
Re-evaluation of the 3 alpha-hydroxysteroid dehydrogenase assay for total bile acids in bile.
Turley, S. D., & Dietschy, J. M. (1978) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)40709-6 · Cited by 519
Redundant Pathways for Negative Feedback Regulation of Bile Acid Production
Wang, L., Lee, Y., Bundman, D. S., Han, Y., Thevananther, S., Kim, C.-S., Chua, S. S., Wei, P. Y., Heyman, R. A., Karin, M., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00187-9 · Cited by 475
Denson, L. A., Sturm, E., Echevarría, W., Zimmerman, T. L., Makishima, M., Mangelsdorf, D. J., & Karpen, S. J. (2001) · Gastroenterology · doi:10.1053/gast.2001.25503 · Cited by 460
Shih, D. Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B. L., Suchy, F. J., Shefer, S., Bollileni, J. S., Gonzalez, F. J., Breslow, J. L., et al. (2001) · Nature Genetics · doi:10.1038/86871 · Cited by 422
Orphan Nuclear Receptors as eLiXiRs and FiXeRs of Sterol Metabolism
Lu, T. T., Repa, J. J., & Mangelsdorf, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r100035200 · Cited by 356
Kerr, T. A., Saeki, S., Schneider, M., Schaefer, K., Berdy, S., Redder, T., Shan, B., Russell, D. W., & Schwarz, M. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00154-5 · Cited by 351
Self-citationSteroid 5α-Reductase 2 Deficiency*
WILSON, J. D., GRIFFIN, J. E., & RUSSELL, D. W. (1993) · Endocrine Reviews · doi:10.1210/edrv-14-5-577 · Cited by 346
Self-citationFORMAN, B. M., Ruan, B. H., Chen, J., Schroepfer, G. J., & Evans, R. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10588 · Cited by 280
Nitta, M., Ku, S., Brown, C., Okamoto, A. Y., & Shan, B. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.6660 · Cited by 279
Disruption of Cholesterol 7α-Hydroxylase Gene in Mice
Schwarz, M., Lund, E. G., Setchell, K. D. R., Kayden, H. J., Zerwekh, J. E., Björkhem, I., Herz, J., & Russell, D. W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.18024 · Cited by 270
Self-citationRosen, H., Reshef, A., Maeda, N., Lippoldt, A., Shpizen, S., Triger, L., Eggertsen, G., Björkhem, I., & Leitersdorf, E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.24.14805 · Cited by 267
Self-citationSchwarz, M., Russell, D. W., Dietschy, J. M., & Turley, S. D. (1998) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32171-4 · Cited by 258
Self-citationHall, J. M., McDonnell, D. P., & Korach, K. S. (2002) · Molecular Endocrinology · doi:10.1210/mend.16.3.0814 · Cited by 249
Disruption of the Oxysterol 7α-Hydroxylase Gene in Mice
Li-Hawkins, J., Lund, E. G., Turley, S. D., & Russell, D. W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001811200 · Cited by 241
Self-citationJeske, D. J., & Dietschy, J. M. (1980) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39816-3 · Cited by 231
Steroid 5 alpha-reductase 2 deficiency
Wilson, J. D. (1993) · Endocrine Reviews · doi:10.1210/er.14.5.577 · Cited by 203
Repa, J. J., Lund, E. G., Horton, J. D., Leitersdorf, E., Russell, D. W., Dietschy, J. M., & Turley, S. D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007653200 · Cited by 202
Self-citationDowling, R. H. (1972) · Gastroenterology · doi:10.1016/s0016-5085(72)80018-0 · Cited by 178
Biotransformation of monoterpenes, bile acids, and other isoprenoids in anaerobic ecosystems
Hylemon, P. B., & Harder, J. (1998) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.1998.tb00382.x · Cited by 156
Schwarz, M., Russell, D. W., Dietschy, J. M., & Turley, S. D. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32213-6 · Cited by 155
Self-citationOn the Turnover and Excretory Products of Cholic and Chenodeoxycholic Acid in Man
Danielsson, H., Eneroth, P. H. E., Hellström, K., Lindstedt, S., & Sjövall, J. (1963) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)67969-x · Cited by 149
Unexpected Virilization in Male Mice Lacking Steroid 5 -Reductase Enzymes
Mahendroo, M., Cala, K. M., Hess, D. L., & Russell, D. W. (2001) · Endocrinology · doi:10.1210/endo.142.11.8510 · Cited by 133
Honda, A., Salen, G., Matsuzaki, Y., BATTA, A. K., Xu, G., Leitersdorf, E., Tint, G. S., Erickson, S. K., Tanaka, N., & Shefer, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103025200 · Cited by 85
Gåfvels, M. E., Olin, M., Chowdhary, B. P., Raudsepp, T., Andersson, U., Persson, B., Jansson, M., Björkhem, I., & Eggertsen, G. (1999) · Genomics · doi:10.1006/geno.1998.5606 · Cited by 72
Self-citationMolecular Cloning and Expression of Rabbit Sterol 12α-Hydroxylase
Eggertsen, G., Olin, M., Andersson, U., Ishida, H., Kubota, S., Hellman, U., Okuda, K., & Björkhem, I. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32269 · Cited by 70
Self-citationHulzebos, C. V., Renfurm, L. N., Bandsma, R., Verkade, H. J., Boer, T. S., Boverhof, R., TANAKA, H. L., Mierau, I., Sauer, P. J. J., Kuipers, F., et al. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31519-4 · Cited by 63
Bramlett, K. S., Yao, S., & Burris, T. P. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3106 · Cited by 56
Genetic analysis of intestinal cholesterol absorption in inbred mice
Schwarz, M., Davis, D. L., Vick, B. R., & Russell, D. W. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31506-6 · Cited by 47
Self-citationAndersson, U., Yang, Y., Björkhem, I., Einarsson, C., Eggertsen, G., & Gåfvels, M. E. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s1388-1981(99)00036-0 · Cited by 44
Self-citation
Cited by
Sorted by citations
Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism
Wahlstrom, A. M., Sayin, S. I., Marschall, H., & Bäckhed, F. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.005 · Cited by 2,969
Sayin, S. I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H.-U., Bamberg, K., Angelin, B., Hyötyläinen, T., Orešič, M., & Bäckhed, F. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.003 · Cited by 2,331
The Enzymes, Regulation, and Genetics of Bile Acid Synthesis
Russell, D. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161712 · Cited by 2,069
Self-citationTargeting bile‐acid signalling for metabolic diseases
Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., & Schoonjans, K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2619 · Cited by 1,422
Chen, M.-L., Yi, L., Zhang, Y., Zhou, X., Ran, L., Yang, J., Zhu, J.-D., Zhang, Q.-Y., & Mi, M.-T. (2016) · mBio · doi:10.1128/mbio.02210-15 · Cited by 754
“the nuclear farnesoid X receptor (FXR) in the ileum and liver (7, 8).”
Background
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
