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FXR Acetylation Is Normally Dynamically Regulated by p300 and SIRT1 but Constitutively Elevated in Metabolic Disease States
Open accessAbstract
The nuclear bile acid receptor FXR is critical for regulation of lipid and glucose metabolism. Here, we report that FXR is a target of SIRT1, a deacetylase that mediates nutritional and hormonal modulation of hepatic metabolism. Lysine 217 of FXR is the major acetylation site targeted by p300 and SIRT1. Acetylation of FXR increases its stability but inhibits heterodimerization with RXRalpha, DNA binding, and transactivation activity. Downregulation of hepatic SIRT1 increased FXR acetylation with deleterious metabolic outcomes. Surprisingly, in mouse models of metabolic disease, FXR interaction with SIRT1 and p300 was dramatically altered, FXR acetylation levels were elevated, and overexpression of SIRT1 or resveratrol treatment reduced acetylated FXR levels. Our data demonstrate that FXR acetylation is normally dynamically regulated by p300 and SIRT1 but is constitutively elevated in metabolic disease states. Small molecules that inhibit FXR acetylation by targeting SIRT1 or p300 may be promising therapeutic agents for metabolic disorders.
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“It has been demonstrated that the gene encoding FMO3 is a direct FXR target gene, and FXR has been found to be a target of sirtuin 1 (SIRT1) in metabolic regulation (23, 34, 35).”
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“Moreover, RSV increased the expression and activity of FMO3 in the liver, corresponding with previously published results (34).”
From Resveratrol Attenuates Trimethylamine- N -Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota (2016) · cites this paper as [34]
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“It has been demonstrated that the gene encoding FMO3 is a direct FXR target gene, and FXR has been found to be a target of sirtuin 1 (SIRT1) in metabolic regulation (23, 34, 35).”
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Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
Lagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057
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
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160
Negative Control of p53 by Sir2α Promotes Cell Survival under Stress
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00524-4 · Cited by 2,081
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
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
Mammalian SIRT1 Represses Forkhead Transcription Factors
Motta, M. C., Divecha, N., Lemieux, M. E., Kamel, C., Chen, D., Gu, W. J., Bultsma, Y., McBurney, M. W., & Guarente, L. (2004) · Cell · doi:10.1016/s0092-8674(04)00126-6 · Cited by 1,366
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 · cited 2×
“, 2006) and protection of intestines from intestinal bacteria growth (Inagaki et al., 2006).”
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Stocke, K. S. (2019) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/3308
Alzaïd, F., Jakobsson, T., Treuter, E., & Venteclef, N. (2019) · Springer eBooks · doi:10.1007/978-3-319-55530-0_116
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Seaman, S., Ruiz, P., Nirello, V. D., Martin-Castilla, L., Elizalde-Garcia, P., Vega-Zuza, A., Vegas-Petrina, L., Lumbreras-Perales, C., Philo, M., Moreno‐Gonzalez, M., et al. (2026) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2026.101813
Zhou, L., Liu, Y., Gu, Q., Du, X., Liu, F., Liu, J., & Xia, C. (2026) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2026.112190
Hamad, R. S., Saber, S., Abdel-Moneim, A.-M. H., Alharbi, M. S., Almansour, O., Alsoqih, N. S., Khodeir, M. M., Hatem, M. M., El-Sayed, M., Rezk, M. Y., et al. (2026) · The FASEB Journal · doi:10.1096/fj.202602105r
Cai, L.-Y., Guan, Y., Hu, J., Sun, C.-Y., Ding, C., Zhang, X., Zeng, X., & Xie, W. (2026) · Liver International · doi:10.1111/liv.70846
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Sjöland, W., & Krautkramer, K. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-19001-8.00031-3
Dereli, E., Bolat, İ., Tekin, S., Bolat, M., & Özdemir, S. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.104065
Kanamaluru, D. (2011) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Self-citationYoon, M. J. (2012) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7ws8r8z
Metadata
- Authors
- Kemper, J. K., Xiao, Z., Ponugoti, B., Miao, J., Fang, S., Kanamaluru, D., Tsang, S., Wu, S.-Y., Chiang, C.-M., & Veenstra, T. D.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Frederick National Laboratory for Cancer Research (US)
- Harold C. Simmons Comprehensive Cancer Center (US)
- Corresponding author
- Kemper, Jongsook Kim
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 10
- Issue
- 5
- Pages
- 392-404
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2785075
- OpenAlex
- W1983620925
- Cited by
- 332
- References
- 39
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 10 · 2023: 15 · 2022: 17 · 2021: 16 · 2020: 22 · 2019: 20 · 2018: 23 · 2017: 22 · 2016: 15 · 2015: 18 · 2014: 29 · 2013: 29 · 2012: 30
- FWCI
- 16.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DigitalCommons-Cedarville (Cedarville University) (submittedVersion)
- Funders
- National Institutes of Health (n01co12400-79-0-22)
- National Cancer Institute (N01CO12400, N01-CO-012400, CA103867, R01CA103867, R01CA124760, CA124760)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK062777, R01DK080032, DK062777, R56DK062777, DK80032)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- farnesoid X receptor, protein acetylation, P300, SIRT1, receptor stability, DNA binding, transcriptional activation, hepatic metabolism, metabolic disorders, resveratrol, small molecule drugs
- MeSH terms
- Resveratrol, Receptor, Farnesoid X-Activated, p300-CBP-Associated Factor, Acetylation, Animals, Disease Models, Animal, Histone Deacetylases, Liver, Liver Diseases, Male, Stilbenes, Transcription Factors, Transcriptional Activation, Down-Regulation, Mutagenesis, Site-Directed, Receptors, Cytoplasmic and Nuclear, Dimerization, RNA, Small Interfering, Retinoid X Receptor alpha, p300-CBP Transcription Factors, Mice, Protein Stability, Sirtuin 1, Hep G2 Cells
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