The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Farnesoid X receptor is essential for normal glucose homeostasis
Open accessAbstract
The bile acid receptor farnesoid X receptor (FXR; NR1H4) is a central regulator of bile acid and lipid metabolism. We show here that FXR plays a key regulatory role in glucose homeostasis. FXR-null mice developed severe fatty liver and elevated circulating FFAs, which was associated with elevated serum glucose and impaired glucose and insulin tolerance. Their insulin resistance was confirmed by the hyperinsulinemic euglycemic clamp, which showed attenuated inhibition of hepatic glucose production by insulin and reduced peripheral glucose disposal. In FXR-/- skeletal muscle and liver, multiple steps in the insulin signaling pathway were markedly blunted. In skeletal muscle, which does not express FXR, triglyceride and FFA levels were increased, and we propose that their inhibitory effects account for insulin resistance in that tissue. In contrast to the results in FXR-/- mice, bile acid activation of FXR in WT mice repressed expression of gluconeogenic genes and decreased serum glucose. The absence of this repression in both FXR-/- and small heterodimer partner-null (SHP-/-) mice demonstrated that the previously described FXR-SHP nuclear receptor cascade also targets glucose metabolism. Taken together, our results identify a link between lipid and glucose metabolism mediated by the FXR-SHP cascade.
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.
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
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
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
Mechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice
Kim, J. K., Gavrilova, O., Chen, Y., Reitman, M. L., & Shulman, G. I. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.8456 · Cited by 443
Seppala-Lindroos, A. (2002) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.7.3023 · Cited by 168
Cited by
TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis
Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., Pruzanski, M., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.001 · Cited by 1,885
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
Gut microbiota in cardiovascular health and disease
Tang, W. H. W., Kitai, T., & Hazen, S. L. (2017) · Circulation Research · doi:10.1161/circresaha.117.309715 · Cited by 1,670
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
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
Dietary lipids, gut microbiota and lipid metabolism
Schoeler, M., & Caesar, R. (2019) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09512-0 · Cited by 1,163
Chávez-Talavera, O., Tailleux, A., Lefebvre, P., & Staels, B. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.055 · Cited by 970
Mudaliar, S., Henry, R. R., Sanyal, A. J., Morrow, L., Marschall, H., Kipnes, M., Adorini, L., Sciacca, C. I., Clopton, P., Castelloe, E., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.05.042 · Cited by 931
FXR is a molecular target for the effects of vertical sleeve gastrectomy
Ryan, K. K., Tremaroli, V., Clemmensen, C., Kovatcheva-Datchary, P., Myronovych, A., Karns, R., Wilson-Pérez, H. E., Sandoval, D. A., Kohli, R., Bäckhed, F., et al. (2014) · Nature · doi:10.1038/nature13135 · Cited by 931
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
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
Li, F., Jiang, C., Krausz, K. W., Li, Y., Albert, I., Hao, H., Fabre, K. M., Mitchell, J. B., Patterson, A. D., & Gonzalez, F. J. (2013) · Nature Communications · doi:10.1038/ncomms3384 · Cited by 705
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
Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease
Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R. G., Krausz, K. W., Cai, J., Qi, Y., Fang, Z.-Z., Takahashi, S., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci76738 · Cited by 693
The Liver as an Endocrine Organ—Linking NAFLD and Insulin Resistance
Watt, M. J., Miotto, P. M., De Nardo, W., & Montgomery, M. K. (2019) · Endocrine Reviews · doi:10.1210/er.2019-00034 · Cited by 615
Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy
Chiang, J. Y. L., & Ferrell, J. M. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00223.2019 · Cited by 580
Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment
Liu, Z., Dai, X., Zhang, H., Shi, R., Hui, Y., Jin, X., Zhang, W., Wang, L., Wang, Q., Wang, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14676-4 · Cited by 549
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
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
The Gut Microbial Endocrine Organ: Bacterially Derived Signals Driving Cardiometabolic Diseases
Brown, J. M., & Hazen, S. L. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-060513-093205 · Cited by 438
Hormonal regulation of hepatic glucose production in health and disease
Lin, H. V., & Accili, D. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.06.003 · Cited by 429
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
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
Pournaras, D. J., Glicksman, C., Vincent, R. P., Kuganolipava, S., Alaghband-Zadeh, J., Mahon, D., Bekker, J. H. R., Ghatei, M. A., Bloom, S. R., Walters, J. R. F., et al. (2012) · Endocrinology · doi:10.1210/en.2011-2145 · Cited by 383
Gut microbiota, enteroendocrine functions and metabolism
Cani, P. D., Everard, A., & Duparc, T. (2013) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2013.09.008 · Cited by 378
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
Kemper, J. K., Xiao, Z., Ponugoti, B., Miao, J., Fang, S., Kanamaluru, D., Tsang, S., Wu, S.-Y., Chiang, C.-M., & Veenstra, T. D. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.009 · Cited by 332
Unraveling the regulation of hepatic gluconeogenesis
Zhang, X., Yang, S., Chen, J., & Su, Z. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00802 · Cited by 314
A selective gut bacterial bile salt hydrolase alters host metabolism
Yao, L., Seaton, S. C., Ndousse-Fetter, S., Adhikari, A. A., DiBenedetto, N., Mina, A. I., Banks, A. S., Bry, L., & Devlin, A. S. (2018) · eLife · doi:10.7554/elife.37182 · Cited by 274
Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis
Adorini, L., Pruzanski, M., & Shapiro, D. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2012.05.012 · Cited by 259
A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
Wei, M., Huang, F., Zhao, L., Zhang, Y., Yang, W., Wang, S., Li, M., Han, X., Ge, K., Qu, C., et al. (2020) · eBioMedicine · doi:10.1016/j.ebiom.2020.102766 · Cited by 253
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
Joyce, S. A., & Gahan, C. G. M. (2016) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-041715-033159 · Cited by 241
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
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
The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases
Fogelson, K. A., Dorrestein, P. C., Zarrinpar, A., & Knight, R. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.02.022 · Cited by 177
Bile Acids, Obesity, and the Metabolic Syndrome
Ma, H., & Patti, M. E. (2014) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2014.07.004 · Cited by 176
Bahne, E., Sun, E. W. L., Young, R. L., Hansen, M., Sonne, D. P., Hansen, J. S., Rohde, U., Liou, A. P., Jackson, M. L., de Fontgalland, D., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.93936 · Cited by 173
Xu, Y., Li, F., Zalzala, M., Xu, J., Gonzalez, F. J., Adorini, L., Lee, Y., Yin, L., & Zhang, Y. (2016) · Hepatology · doi:10.1002/hep.28712 · Cited by 172
Zhao, X., Peter, A., Fritsche, J., Elcnerova, M., Fritsche, A., Häring, H.-U., Schleicher, E. D., Xu, G., & Lehmann, R. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90748.2008 · Cited by 170
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
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
Simonen, M., Dali-Youcef, N., Kaminska, D., Venesmaa, S., Käkelä, P., Pääkkönen, M., Hallikainen, M., Kolehmainen, M., Uusitupa, M., Moilanen, L., et al. (2012) · Obesity Surgery · doi:10.1007/s11695-012-0673-5 · Cited by 145
Understanding bile acid signaling in diabetes: From pathophysiology to therapeutic targets
Ferrell, J. M., & Chiang, J. Y. L. (2019) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2019.0043 · Cited by 139
Colesevelam lowers glucose and lipid levels in type 2 diabetes: The clinical evidence
Fonseca, V. A., Handelsman, Y., & Staels, B. (2010) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2009.01181.x · Cited by 130
Tiwari, A., & Maiti, P. (2009) · Drug Discovery Today · doi:10.1016/j.drudis.2009.02.005 · Cited by 122
Ferrell, J. M., Boehme, S., Li, F., & Chiang, J. Y. L. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m064709 · Cited by 112
Identification of Novel Pathways That Control Farnesoid X Receptor-mediated Hypocholesterolemia
Zhang, Y., Yin, L., Anderson, J., Ma, H., Gonzalez, F. J., Willson, T. M., & Edwards, P. A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.083899 · Cited by 112
Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice
Kim, K. H., Choi, S., Zhou, Y., Kim, E. Y., Lee, J. M., Saha, P. K., Anakk, S., & Moore, D. D. (2017) · Hepatology · doi:10.1002/hep.29199 · Cited by 107
Bazzari, F. H., Abdallah, D. M., & El-Abhar, H. S. (2019) · Molecules · doi:10.3390/molecules24101992 · Cited by 98
Bile acids: From digestion to cancers
Baptissart, M., Vega, A., Maqdasy, S., Caira, F., Baron, S., Lobaccaro, J.-M. A., & Volle, D. H. (2013) · Biochimie · doi:10.1016/j.biochi.2012.06.022 · Cited by 97
Nuclear receptors linking metabolism, inflammation, and fibrosis in nonalcoholic fatty liver disease
Puengel, T., Liu, H., Guillot, A., Heymann, F., Tacke, F., & Peiseler, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052668 · Cited by 95
Mechanism of glucose-lowering by metformin in type 2 diabetes: Role of bile acids
Sansome, D. J., Xie, C., Veedfald, S., Horowitz, M., Rayner, C. K., & Wu, T. (2020) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13869 · Cited by 84
The 'forgotten' bile acid sequestrants: is now a good time to remember?
Bays, H. E., & Goldberg, R. B. (2007) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e31815a69fc · Cited by 83
Nonsteroidal FXR Ligands: Current Status and Clinical Applications
Gege, C., Hambruch, E., Hambruch, N., Kinzel, O., & Kremoser, C. (2019) · Handbook of Experimental Pharmacology · doi:10.1007/164_2019_232 · Cited by 83
Role of bile acids in the regulation of the metabolic pathways
Taoka, H., Yokoyama, Y., Morimoto, K., Kitamura, N., Tanigaki, T., Takashina, Y., Tsubota, K., & Watanabe, M. (2016) · World Journal of Diabetes · doi:10.4239/wjd.v7.i13.260 · Cited by 80
Miyata, M., Sakaida, Y., Matsuzawa, H., Yoshinari, K., & Yamazoe, Y. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.1885 · Cited by 77
Miyata, M., Takamatsu, Y., Kuribayashi, H., & Yamazoe, Y. (2009) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.160093 · Cited by 72
New Insights Into the Anti-Diabetic Actions of Metformin: From the Liver to the Gut
Wu, T., Horowitz, M., & Rayner, C. K. (2017) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2017.1273769 · Cited by 64
Ploton, M., Mazuy, C., Gheeraert, C., Dubois, V., Berthier, A., Dubois-Chevalier, J., Maréchal, X., Bantubungi, K., Diemer, H., Cianférani, S., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.06.022 · Cited by 63
Renga, B., Mencarelli, A., Migliorati, M., Cipriani, S., D’Amore, C., Distrutti, E., & Fiorucci, S. (2011) · Inflammation Research · doi:10.1007/s00011-010-0306-1 · Cited by 53
MASLD treatment—a shift in the paradigm is imminent
Machado, M. V. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1316284 · Cited by 51
Bacterial metabolites directly modulate farnesoid X receptor activity
Zhang, X., Osaka, T., & Tsuneda, S. (2015) · Nutrition & Metabolism · doi:10.1186/s12986-015-0045-y · Cited by 34
Farnesoid X receptor alpha: a molecular link between bile acids and steroid signaling
Baptissart, M., Vega, A., Martinot, E., Baron, S., Lobaccaro, J.-M. A., & Volle, D. H. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1387-0 · Cited by 32
Microbial factors in inflammatory diseases and cancers
Ong, H. S., & Yim, H. C. H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-5987-2_7 · Cited by 29
On the Pharmacology of Farnesoid X Receptor Agonists: Give me an "A", Like in "Acid"
Hambruch, E., Kinzel, O., & Kremoser, C. (2016) · Nuclear Receptor Research · doi:10.11131/2016/101207 · Cited by 3
Metadata
- Authors
- Ma, K.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-03-23
- Volume
- 116
- Issue
- 4
- Pages
- 1102-1109
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2142427646
- Cited by
- 882
- References
- 4
- FWCI
- 17.67
- Type
- journal article
- Language
- en
- Open access
- bronze
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
