Cited by 2,714Drug Transport and Resistance MechanismsCholesterol and Lipid MetabolismPeroxisome Proliferator-Activated Receptors

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Identification of a Nuclear Receptor for Bile Acids

Makishima, Makoto, Okamoto, Arthur Y., Repa, Joyce J., Tu, Hua, Learned, R. Marc, Luk, Alvin, Hull, Mitchell V., Lustig, Kevin D., Mangelsdorf, David J., Shan, Bei·1999·Science

DOI 10.1126/science.284.5418.1362

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1126/science.284.5418.1362

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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 RXR heterodimers and orphan receptors
Mangelsdorf, D. J., & Evans, R. M. (1995) · Cell · doi:10.1016/0092-8674(95)90200-7 · Cited by 3,165
Self-citation
Sequence and Characterization of a Coactivator for the Steroid Hormone Receptor Superfamily
Oñate, S. A., Tsai, S. Y., Tsai, M., & O’Malley, B. W. (1995) · Science · doi:10.1126/science.270.5240.1354 · Cited by 2,398
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
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
Self-citation
Cholesterol and Bile Acid Metabolism Are Impaired in Mice Lacking the Nuclear Oxysterol Receptor LXRα
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 1,466
Self-citation
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
LXR, a nuclear receptor that defines a distinct retinoid response pathway.Preprint
Willy, P. J., Umesono, K., Ong, E. S., Evans, R. M., Heyman, R. A., & Mangelsdorf, D. J. (1995) · Genes & Development · doi:10.1101/gad.9.9.1033 · Cited by 1,138
Self-citation
Bile acid biosynthesis
Russell, D. W., & Setchell, K. D. R. (1992) · Biochemistry · doi:10.1021/bi00135a001 · Cited by 819
Nuclear receptor coactivators
Glass, C. K., Rose, D. W., & Rosenfeld, M. G. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80066-x · Cited by 691

Show all 20 references

Research works printed but not linked: 6

Seol W., Choi H.-S., Moore D. D., Mol. Endocrinol. 9, 72 (1995).
LaRusso N. F., Hoffman N. E., Hofmann A. F., Northfield T. C., Thistle J. L., Gastroenterology 69, 1301 (1975).
Darimont B. D., et al., ibid. 12, 3343 (1998);
J. R. Crowther ELISA: Theory and Practice vol. 42 in Methods in Molecular Biology (Humana Totowa NJ 1995).
Wong M. H., Oelkers P., Dawson P. A., ibid. 270, 27228 (1995) ;
Craddock A. L., et al., Am. J. Physiol. 274, G157 (1998).

Sorted by citations

Gut microbiota in human metabolic health and disease
Fan, Y., & Pedersen, O. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0433-9 · Cited by 4,724
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., et al. (2006) · Nature · doi:10.1038/nature04330 · Cited by 2,220
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
Obesity and inflammation: the linking mechanism and the complications
Ellulu, M. S., Patimah, I., Khaza’ai, H., Rahmat, A., & Abed, Y. (2017) · Archives of Medical Science · doi:10.5114/aoms.2016.58928 · Cited by 1,982
Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis
Jia, W., Xie, G., & Jia, W. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.119 · Cited by 1,924
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
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678
A G Protein-coupled Receptor Responsive to Bile Acids
Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., Fukusumi, S., Habata, Y., Itoh, T., Shintani, Y., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209706200 · Cited by 1,628
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
Self-citation
Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host
Khovidhunkit, W., Kim, M.-S., Memon, R. A., Shigenaga, J. K., Moser, A. H., Feingold, K. R., & Grunfeld, C. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r300019-jlr200 · Cited by 1,481
Targeting 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
Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280
Pleiotropic Roles of Bile Acids in Metabolism
de Aguiar Vallim, T. Q., Tarling, E. J., & Edwards, P. A. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.013 · Cited by 1,209
Bile acids and the gut microbiota: metabolic interactions and impacts on disease
Collins, S. L., Stine, J. G., Bisanz, J. E., Okafor, C. D., & Patterson, A. D. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00805-x · Cited by 1,214
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
Inagaki, T., Moschetta, A., Lee, Y.-K., Peng, L., Zhao, G., Downes, M., Yu, R. T., Shelton, J. M., Richardson, J. A., Repa, J. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509592103 · Cited by 1,164
Self-citation
Vitamin D Receptor As an Intestinal Bile Acid Sensor
Makishima, M., Lu, T. T., Xie, W., Whitfield, G. K., Domoto, H., Evans, R. M., Haussler, M. R., & Mangelsdorf, D. J. (2002) · Science · doi:10.1126/science.1070477 · Cited by 1,176
Self-citation
Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
Song, X., Sun, X., Oh, S. F., Wu, M., Zhang, Y., Zheng, W., Geva-Zatorsky, N., Jupp, R., Mathis, D., Benoist, C., et al. (2020) · Nature · doi:10.1038/s41586-019-1865-0 · Cited by 1,024
Identification of membrane-type receptor for bile acids (M-BAR)
Maruyama, T., Miyamoto, Y., Nakamura, T., Tamai, Y., Okada, H., Sugiyama, E., Nakamura, T., Itadani, H., & Tanaka, K. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02550-0 · Cited by 993
Bile salt transporters: molecular characterization, function, and regulation
Trauner, M., & Boyer, J. L. (2003) · Physiological Reviews · doi:10.1152/physrev.00027.2002 · Cited by 999
Bile acid signaling in metabolic disease and drug therapy
Li, T., & Chiang, J. Y. L. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008201 · Cited by 935
Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor
Kast, H. R., Goodwin, B., Tarr, P. T., Jones, S. A., Anisfeld, A. M., Stoltz, C. M., Tontonoz, P., Kliewer, S., Willson, T. M., & Edwards, P. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109326200 · Cited by 916
Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876
“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).”
Background
Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR
Calkin, A. C., & Tontonoz, P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3312 · Cited by 779
Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance
Fang, S., Suh, J. M., Reilly, S. M., Yu, E., Osborn, O., Lackey, D., Yoshihara, E., Perino, A., Jacinto, S., Lukasheva, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3760 · Cited by 738
6α-Ethyl-Chenodeoxycholic Acid (6-ECDCA), a Potent and Selective FXR Agonist Endowed with Anticholestatic Activity
Pellicciari, R., Fiorucci, S., Camaioni, E., Clerici, C., Costantino, G., Maloney, P. R., Morelli, A., Parks, D. J., & Willson, T. M. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm025529g · Cited by 743
Bile acids as regulatory molecules
Hylemon, P. B., Zhou, H., Pandak, W. M., Ren, S., Gil, G., & Dent, P. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900007-jlr200 · Cited by 694
Bile acid receptors as targets for drug development
Schaap, F. G., Trauner, M., & Jansen, P. L. M. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.151 · Cited by 696
The bile acid receptor FXR is a modulator of intestinal innate immunity
Vavassori, P., Mencarelli, A., Renga, B., Distrutti, E., & Fiorucci, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803978 · Cited by 655
Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives
Arab, J. P., Karpen, S. J., Dawson, P. A., Arrese, M., & Trauner, M. (2017) · Hepatology · doi:10.1002/hep.28709 · Cited by 634
Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid
Hirschfield, G. M., Mason, A., Luketic, V., Lindor, K., Gordon, S. C., Mayo, M., Kowdley, K. V., Vincent, C., Bodhenheimer, H. C., Parés, A., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.12.005 · Cited by 576
New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond
Beuers, U., Trauner, M., Jansen, P., & Poupon, R. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.023 · Cited by 537
Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders
Fiorucci, S., & Distrutti, E. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.09.001 · Cited by 539
Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome
Song, Z., Cai, Y., Lao, X., Wang, X., Lin, X., Cui, Y., Kalavagunta, P. K., Liao, J., Jin, L., Shang, J., et al. (2019) · Microbiome · doi:10.1186/s40168-019-0628-3 · Cited by 505
Bile Acids Induce Inflammatory Genes in Hepatocytes
Allen, K., Jaeschke, H., & Copple, B. L. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2010.11.026 · Cited by 501
Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor
Yang, F., Huang, X., Yi, T., Yen, Y., Moore, D. D., & Huang, W. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1078 · Cited by 488
Bile acid nuclear receptor FXR and digestive system diseases
Ding, L., Yang, L., Wang, Z., & Huang, W. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.01.004 · Cited by 477
The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis
Fiorucci, S., Antonelli, E., Rizzo, G., Renga, B., Mencarelli, A., Riccardi, L., Orlandi, S., Pellicciari, R., & Morelli, A. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.08.001 · Cited by 472
Molecular physiology of bile acid signaling in health, disease, and aging
Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481
Interactions between Bacteria and Bile Salts in the Gastrointestinal and Hepatobiliary Tracts
Urdaneta, V., & Casadesús, J. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00163 · Cited by 449
Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice
Kong, B., Wang, L., Chiang, J. Y. L., Zhang, Y., Klaassen, C. D., & Guo, G. L. (2012) · Hepatology · doi:10.1002/hep.25740 · Cited by 456
The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation
Pols, T. W. H., Noriega, L. G., Nomura, M., Auwerx, J., & Schoonjans, K. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2010.12.004 · Cited by 454
Microbial modulation of cardiovascular disease
Brown, J. M., & Hazen, S. L. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.149 · Cited by 440
Human Insulin Resistance Is Associated With Increased Plasma Levels of 12α-Hydroxylated Bile Acids
Haeusler, R. A., Astiarraga, B., Camastra, S., Accili, D., & Ferrannini, E. (2013) · Diabetes · doi:10.2337/db13-0639 · Cited by 444
The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids
Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P. K., Cazanave, S., Luketic, V. A., Siddiqui, M. S., Boyett, S., Min, H., et al. (2018) · Hepatology · doi:10.1002/hep.29359 · Cited by 426
Expression and function of the bile acid receptor TGR5 in Kupffer cells
Keitel, V., Donner, M., Winandy, S., Kubitz, R., & Häussinger, D. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.04.171 · Cited by 418
Bile Acids as Hormones: The FXR-FGF15/19 Pathway
Kliewer, S. A., & Mangelsdorf, D. J. (2015) · Digestive Diseases · doi:10.1159/000371670 · Cited by 424
Self-citation
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415
FXR: a metabolic regulator and cell protector
Wang, Y.-D., Chen, W.-D., Moore, D. D., & Huang, W. (2008) · Cell Research · doi:10.1038/cr.2008.289 · Cited by 389
FXR, a multipurpose nuclear receptor
Lee, F. Y., Lee, H., Hubbert, M. L., Edwards, P. A., & Zhang, Y. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.08.002 · Cited by 344
Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes
Claus, S. P., Tsang, T. M., Wang, Y., Cloarec, O., Skordi, E., Martin, F., Rezzi, S., Ross, A., Kochhar, S., Holmes, E., et al. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.56 · Cited by 334
A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis
Ratziu, V., de Ledinghen, V., Oberti, F., Mathurin, P., Wartelle-Bladou, C., Renou, C., Sogni, P., Maynard, M., Larrey, D., Serfaty, L., et al. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2010.08.030 · Cited by 338
Bile acids as endogenous etiologic agents in gastrointestinal cancer
Bernstein, H., Bernstein, C., Payne, C. M., & Dvorak, K. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.3329 · Cited by 340
Inhibiting the Initiation of Clostridium difficile Spore Germination using Analogs of Chenodeoxycholic Acid, a Bile Acid
Sorg, J. A., & Sonenshein, A. L. (2010) · Journal of Bacteriology · doi:10.1128/jb.00610-10 · Cited by 332
Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens
Ridlon, J. M., Ikegawa, S., Alves, J. M. P., Zhou, B., Kobayashi, A., Iida, T., Mitamura, K., Tanabe, G., Serrano, M., De Guzman, A., et al. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m038869 · Cited by 319
Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity
Guo, G. L., Lambert, G., Negishi, M., Ward, J. M., Brewer, H. B., Kliewer, S. A., Gonzalez, F. J., & Sinal, C. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307145200 · Cited by 312
Primary biliary cholangitis: pathogenesis and therapeutic opportunities
Gulamhusein, A. F., & Hirschfield, G. M. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0226-7 · Cited by 308
Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis
Zhang, S., Wang, J., Liu, Q., & Harnish, D. C. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.03.025 · Cited by 290
Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects
di Masi, A., Marinis, E. D., Ascenzi, P., & Marino, M. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2009.04.002 · Cited by 288
Bile acid signaling pathways from the enterohepatic circulation to the central nervous system
Mertens, K. L., Kalsbeek, A., Soeters, M. R., & Eggink, H. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00617 · Cited by 287
Bile acids are nutrient signaling hormones
Zhou, H., & Hylemon, P. B. (2014) · Steroids · doi:10.1016/j.steroids.2014.04.016 · Cited by 285
Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasis
Modica, S., Petruzzelli, M., Bellafante, E., Murzilli, S., Salvatore, L., Celli, N., Di Tullio, G., Palasciano, G., Moustafa, T., Halilbasic, E., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.10.028 · Cited by 275
Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats
Verbeke, L., Farre, R., Trebicka, J., Komuta, M., Roskams, T., Klein, S., Elst, I. V., Windmolders, P., Vanuytsel, T., Nevens, F., et al. (2014) · Hepatology · doi:10.1002/hep.26939 · Cited by 258
Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism
Eloranta, J. J., & Kullak-Ublick, G. A. (2005) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.09.019 · Cited by 260
The Role of Bile Acids in Glucose Metabolism and Their Relation with Diabetes
Alberto González-Regueiro, J., Moreno-Castañeda, L., Uribe, M., & Carlos Chávez-Tapia, N. (2017) · Annals of Hepatology · doi:10.5604/01.3001.0010.5494 · Cited by 247
Cholic acid mediates negative feedback regulation of bile acid synthesis in mice
Li-Hawkins, J., Gåfvels, M., Olin, M., Lund, E. G., Andersson, U., Schuster, G., Björkhem, I., Russell, D. W., & Eggertsen, G. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216309 · Cited by 227
New therapeutic concepts in bile acid transport and signaling for management of cholestasis
Trauner, M., Fuchs, C. D., Halilbasic, E., & Paumgartner, G. (2017) · Hepatology · doi:10.1002/hep.28991 · Cited by 227
Metabolic Messengers: bile acids
Perino, A., & Schoonjans, K. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00559-z · Cited by 223
Intestinal absorption of bile acids in health and disease
Ticho, A. L., Malhotra, P., Dudeja, P. K., Gill, R. K., & Alrefai, W. A. (2019) · Comprehensive physiology · doi:10.1002/cphy.c190007 · Cited by 215
The biosynthesis, signaling, and neurological functions of bile acids
Kiriyama, Y., & Nochi, H. (2019) · Biomolecules · doi:10.3390/biom9060232 · Cited by 204
Novel therapeutic targets for cholestatic and fatty liver disease
Trauner, M., & Fuchs, C. D. (2022) · Gut · doi:10.1136/gutjnl-2021-324305 · Cited by 204
Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway
Sun, R., Yang, N., Kong, B., Cao, B., Feng, D., Yu, X., Ge, C., Huang, J., Shen, J., Wang, P., et al. (2017) · Molecular Pharmacology · doi:10.1124/mol.116.106617 · Cited by 199
D3R grand challenge 2: blind prediction of protein–ligand poses, affinity rankings, and relative binding free energies.
Gaieb, Z., Liu, S., Gathiaka, S., Chiu, M., Yang, H., Shao, C., Feher, V. A., Walters, W. P., Kuhn, B., Rudolph, M. G., et al. (2018) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-017-0088-4 · Cited by 193
The Human Apolipoprotein AV Gene Is Regulated by Peroxisome Proliferator-activated Receptor-α and Contains a Novel Farnesoid X-activated Receptor Response Element
Prieur, X., Coste, H., & Rodríguez, J. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301302200 · Cited by 194
Host genotype and gut microbiome modulate insulin secretion and diet-induced metabolic phenotypes
Kreznar, J. H., Keller, M. P., Traeger, L. L., Rabaglia, M. E., Schueler, K. L., Stapleton, D. S., Zhao, W., Vivas, E. I., Yandell, B. S., Broman, A. T., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.062 · Cited by 177
The bile acid membrane receptor TGR5: a valuable metabolic target
Pols, T. W. H., Noriega, L. G., Nomura, M., Auwerx, J., & Schoonjans, K. (2011) · Digestive Diseases · doi:10.1159/000324126 · Cited by 185
Molecular basis of bile acid-FXR-FGF15/19 signaling axis
Katafuchi, T., & Makishima, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116046 · Cited by 193
Self-citation
The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice
de Wit, N. J., Bosch-Vermeulen, H., de Groot, P. J., Hooiveld, G. J., Bromhaar, M. M. G., Jansen, J., Müller, M., & van der Meer, R. (2008) · BMC Medical Genomics · doi:10.1186/1755-8794-1-14 · Cited by 182
Gut microbiota remodeling reverses aging-associated inflammation and dysregulation of systemic bile acid homeostasis in mice sex-specifically
Ma, J., Hong, Y., Zheng, N., Xie, G., Lyu, Y., Gu, Y., Xi, C., Chen, L., Wu, G., Li, Y., et al. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1763770 · Cited by 171
Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis
Baghdasaryan, A., Fuchs, C. D., Österreicher, C. H., Lemberger, U. J., Halilbasic, E., Påhlman, I., Graffner, H., Krones, E., Fickert, P., Wahlström, A., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.10.024 · Cited by 187
Bile acid signaling in neurodegenerative and neurological disorders
Grant, S. M., & DeMorrow, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21175982 · Cited by 185
A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis
Fiorucci, S., Rizzo, G., Antonelli, E., Renga, B., Mencarelli, A., Riccardi, L., Orlandi, S., Pruzanski, M., Morelli, A., & Pellicciari, R. (2005) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.084905 · Cited by 183
Bile acids and their receptors
Martinot, E., Sèdes, L., Baptissart, M., Lobaccaro, J.-M., Caira, F., Beaudoin, C., & Volle, D. H. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.01.006 · Cited by 162
The bile acid sensor farnesoid X receptor is a modulator of liver immunity in a rodent model of acute hepatitis
Mencarelli, A., Renga, B., Migliorati, M., Cipriani, S., Distrutti, E., Santucci, L., & Fiorucci, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901347 · Cited by 177
Identification of Farnesoid X Receptor β as a Novel Mammalian Nuclear Receptor Sensing Lanosterol
Otte, K., Kranz, H., Kober, I., Thompson, P., Hoefer, M., Haubold, B., Remmel, B., Voss, H., Kaiser, C., Albers, M., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.3.864-872.2003 · Cited by 176
Cross-Talk between Farnesoid-X-Receptor (FXR) and Peroxisome Proliferator-Activated Receptor γ Contributes to the Antifibrotic Activity of FXR Ligands in Rodent Models of Liver Cirrhosis
Fiorucci, S., Rizzo, G., Antonelli, E., Renga, B., Mencarelli, A., Riccardi, L., Morelli, A., Pruzanski, M., & Pellicciari, R. (2005) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.085597 · Cited by 177
Nuclear receptors in bile acid metabolism
Li, T., & Chiang, J. Y. L. (2013) · Drug Metabolism Reviews · doi:10.3109/03602532.2012.740048 · Cited by 176
Farnesoid x receptor ligands inhibit vascular smooth muscle cell inflammation and migration
Li, Y. T. Y., Swales, K. E., Thomas, G. J., Warner, T. D., & Bishop-Bailey, D. (2007) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.152694 · Cited by 171
Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity
Ahmad, N. N., Pfalzer, A., & Kaplan, L. M. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.38 · Cited by 163
SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis
Zhou, J., Cui, S., He, Q., Guo, Y., Pan, X., Zhang, P., Huang, N., Ge, C., Wang, G., Gonzalez, F. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14138-6 · Cited by 154
Bile acids and bariatric surgery
Albaugh, V. L., Banan, B., Ajouz, H., Abumrad, N. N., & Flynn, C. R. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.001 · Cited by 148
Mechanisms of disease: inborn errors of bile acid synthesis
Sundaram, S. S., Bove, K. E., Lovell, M. A., & Sokol, R. J. (2008) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep1179 · Cited by 146
The Lactobacillus Bile Salt Hydrolase Repertoire Reveals Niche-Specific Adaptation
O’Flaherty, S., Briner Crawley, A., Theriot, C. M., & Barrangou, R. (2018) · mSphere · doi:10.1128/msphere.00140-18 · Cited by 118
Prevention of spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice by intestinal-specific farnesoid X receptor reactivation
Degirolamo, C., Modica, S., Vacca, M., Di Tullio, G., Morgano, A., D'Orazio, A., Kannisto, K., Parini, P., & Moschetta, A. (2015) · Hepatology · doi:10.1002/hep.27274 · Cited by 121
TGR5: an emerging bile acid G-protein-coupled receptor target for the potential treatment of metabolic disorders
Tiwari, A., & Maiti, P. (2009) · Drug Discovery Today · doi:10.1016/j.drudis.2009.02.005 · Cited by 122
Probiotics and the BSH-related cholesterol lowering mechanism: a Jekyll and Hyde scenario
Choi, S.-B., Lew, L.-C., Yeo, S.-K., Nair Parvathy, S., & Liong, M.-T. (2015) · Critical Reviews in Biotechnology · doi:10.3109/07388551.2014.889077 · Cited by 119
Short-chain fatty acids, secondary bile acids and indoles: gut microbial metabolites with effects on enteroendocrine cell function and their potential as therapies for metabolic disease
Masse, K. E., & Lu, V. B. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1169624 · Cited by 120
“The functional role of FXR activation is well documented (120, 136, 137).”
Background
Farnesoid X Receptor Alleviates Age-Related Proliferation Defects in Regenerating Mouse Livers by Activating Forkhead Box M1b Transcription
Chen, W.-D., Wang, Y.-D., Zhang, L., Shiah, S., Wang, M., Yang, F., Yu, D., Forman, B. M., & Huang, W. (2010) · Hepatology · doi:10.1002/hep.23390 · Cited by 115
Microbiota-gut-brain axis: enteroendocrine cells and the enteric nervous system form an interface between the microbiota and the central nervous system
KUWAHARA, A., MATSUDA, K., KUWAHARA, Y., ASANO, S., INUI, T., & MARUNAKA, Y. (2020) · Biomedical Research · doi:10.2220/biomedres.41.199 · Cited by 112
Nuclear receptor-mediated repression of human cholesterol 7α-hydroxylase gene transcription by bile acids
Chen, W., Owsley, E., Yang, Y., Stroup, D., & Chiang, J. Y. L. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30272-8 · Cited by 112

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.
ORCID: Makishima, Makoto
Repa, Joyce J.
Tu, Hua
Hull, Mitchell V.
Mangelsdorf, David J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1999-05-21
Volume: 284
Issue: 5418
Pages: 1362-1365
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.284.5418.1362
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › 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

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

Identification of a Nuclear Receptor for Bile Acids

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks