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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FXR is a target of SIRT1 in metabolic regulation.
“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).”
RSV increased the expression and activity of FMO3 in the liver.
“Moreover, RSV increased the expression and activity of FMO3 in the liver, corresponding with previously published results (34).”
The gene encoding FMO3 is a direct FXR target gene.
“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 · see citing works
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 · see citing works
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 · see citing works
The RXR heterodimers and orphan receptors
Mangelsdorf, D. J., & Evans, R. M. (1995) · Cell · doi:10.1016/0092-8674(95)90200-7 · Cited by 3,133 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 1,351 · see citing works
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 · see citing works
Rosenfeld, M. G., Lunyak, V. V., & Glass, C. K. (2006) · Genes & Development · doi:10.1101/gad.1424806 · Cited by 952 · see citing works
Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice
Zhang, Y., Lee, F. Y., Barrera, G., Lee, H., Vales, C., Gonzalez, F. J., Willson, T. M., & Edwards, P. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506982103 · Cited by 951 · see citing works
Farnesoid X receptor is essential for normal glucose homeostasis
Ma, K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25604 · Cited by 883 · see citing works
Tip60-Dependent Acetylation of p53 Modulates the Decision between Cell-Cycle Arrest and Apoptosis
Tang, Y., Luo, J., Zhang, W., & Gu, W. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.11.021 · Cited by 724 · see citing works
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 · see citing works
SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosisPreprint
Vaquero, A., Scher, M. B., Lee, D. H., Sutton, A., Cheng, H.-L., Alt, F. W., Serrano, L., Sternglanz, R., & Reinberg, D. (2006) · Genes & Development · doi:10.1101/gad.1412706 · Cited by 670 · see citing works
Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration
Huang, W., Ma, K., Zhang, J., Qatanani, M., Cuvillier, J., Liu, J., Dong, B., Huang, X., & Moore, D. D. (2006) · Science · doi:10.1126/science.1121435 · Cited by 645 · see citing works
SIRT1 Deacetylates and Positively Regulates the Nuclear Receptor LXR
Li, X., Zhang, S., Blander, G., Tse, J. G., Krieger, M., & Guarente, L. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.032 · Cited by 631 · see citing works
LXRS AND FXR: The Yin and Yang of Cholesterol and Fat Metabolism
Kalaany, N. Y., & Mangelsdorf, D. J. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.68.033104.152158 · Cited by 619 · see citing works
Daitoku, H., Hatta, M., Matsuzaki, H., Aratani, S., Ohshima, T., Miyagishi, M., Nakajima, T., & Fukamizu, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400593101 · Cited by 602 · see citing works
Metabolic adaptations through the PGC‐1α and SIRT1 pathways
Rodgers, J. T., Lerín, C., Gerhart‐Hines, Z., & Puigserver, P. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.11.034 · Cited by 599 · see citing works
FoxO1 protects against pancreatic β cell failure through NeuroD and MafA induction
Kitamura, Y., Kitamura, T., Kruse, J.-P., Raum, J. C., Stein, R. W., Gu, W. J., & Accili, D. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.08.004 · Cited by 552 · see citing works
Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1
Rodgers, J. T., & Puigserver, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702509104 · Cited by 549 · see citing works
Lerin, C., Rodgers, J. T., Kalume, D. E., Kim, S.-H., Pandey, A., & Puigserver, P. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.013 · Cited by 443 · see citing works
Sirtuins in Aging and DiseasePreprint
Guarente, L. (2007) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2007.72.024 · Cited by 371 · see citing works
Zhang, Y., Castellani, L. W., Sinal, C. J., Gonzalez, F. J., & Edwards, P. A. (2004) · Genes & Development · doi:10.1101/gad.1138104 · Cited by 367 · see citing works
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 · see citing works
Bhalla, S., Özalp, V. C., Fang, S., Xiang, L., & Kemper, J. K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405423200 · Cited by 228 · see citing works
Self-citationMiao, J., Fang, S., Bae, Y., & Kemper, J. K. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510713200 · Cited by 197 · see citing works
Self-citationFXR: a promising target for the metabolic syndrome?
Cariou, B., & Staels, B. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.03.002 · Cited by 153 · see citing works
Miao, J., Xiao, Z., Kanamaluru, D., Min, G., Yau, P. M., Veenstra, T. D., Ellis, E. C. S., Strom, S., Suino-Powell, K. M., Xu, H. E., et al. (2009) · Genes & Development · doi:10.1101/gad.1773909 · Cited by 126 · see citing works
Self-citationDent, P., Fang, Y., Gupta, S., Studer, E. J., Mitchell, C., Spiegel, S., & Hylemon, P. B. (2005) · Hepatology · doi:10.1002/hep.20942 · Cited by 125 · see citing works
Willson, T. M., Jones, S. A., Moore, J. T., & Kliewer, S. A. (2001) · Medicinal Research Reviews · doi:10.1002/med.1023 · Cited by 110 · see citing works
Kemper, J. K., Kim, H., Miao, J., Bhalla, S., & Bae, Y. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.17.7707-7719.2004 · Cited by 104 · see citing works
Self-citationPGC-1α Activates CYP7A1 and Bile Acid Biosynthesis
Shin, D.-J., Campos-Sandoval, J. A., Gil, G., & Osborne, T. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m309736200 · Cited by 102 · see citing works
Fang, S., Miao, J., Xiang, L., Ponugoti, B., Treuter, E., & Kemper, J. K. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00944-06 · Cited by 101 · see citing works
Self-citationPhosphorylation of Farnesoid X Receptor by Protein Kinase C Promotes Its Transcriptional Activity
Gineste, R., Sirvent, A., Paumelle, R., Helleboid, S., Aquilina, A., Darteil, R., Hum, D. W., Fruchart, J., & Staels, B. (2008) · Molecular Endocrinology · doi:10.1210/me.2008-0092 · Cited by 79 · see citing works
The p300 Acetylase Is Critical for Ligand-activated Farnesoid X Receptor (FXR) Induction of SHP
Fang, S., Tsang, S., Jones, R., Ponugoti, B., Yoon, H., Wu, S.-Y., Chiang, C., Willson, T. M., & Kemper, J. K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803531200 · Cited by 75 · see citing works
Self-citationSinclair, D. A., Lin, S.-J., & Guarente, L. (2006) · Science · doi:10.1126/science.312.5771.195d · Cited by 36 · see citing works
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Rui, L. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130024 · Cited by 2,258 · see citing works
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238 · see citing works
MicroRNAs in metabolism and metabolic disorders
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SIRT1 and other sirtuins in metabolism
Chang, H.-C., & Guarente, L. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.001 · Cited by 1,138 · see citing works
Chávez-Talavera, O., Tailleux, A., Lefebvre, P., & Staels, B. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.055 · Cited by 970 · see citing works
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 · see citing works
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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 · see citing works
Self-citationMetabolites as regulators of insulin sensitivity and metabolism
Yang, Q., Vijayakumar, A., & Kahn, B. B. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0044-8 · Cited by 681 · see citing works
Fleishman, J. S., & Kumar, S. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01811-6 · Cited by 577 · see citing works
SIRT1 Deacetylates and Inhibits SREBP-1C Activity in Regulation of Hepatic Lipid Metabolism*
Ponugoti, B., Kim, D.-H., Xiao, Z., Smith, Z., Miao, J., Zang, M., Wu, S.-Y., Chiang, C., Veenstra, T. D., & Kemper, J. K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.122978 · Cited by 545 · see citing works
Self-citationGuarente, L. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1100831 · Cited by 510 · see citing works
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Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481 · see citing works
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Hao, H., Cao, L., Jiang, C., Che, Y., Zhang, S., Takahashi, S., Wang, G., & Gonzalez, F. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.007 · Cited by 479 · see citing works
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Guarente, L. (2013) · Genes & Development · doi:10.1101/gad.227439.113 · Cited by 464 · see citing works
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Shapiro, H., Kolodziejczyk, A. A., Halstuch, D., & Elinav, E. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171965 · Cited by 467 · see citing works
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 · see citing works
Beyond intestinal soap—bile acids in metabolic control
Kuipers, F., Bloks, V. W., & Groen, A. K. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.60 · Cited by 453 · see citing works
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Seok, S., Fu, T., Choi, S., Yang, L., Zhu, R., Kumar, S., Sun, X., Yoon, G., KANG, Y. Y., Zhong, W., et al. (2014) · Nature · doi:10.1038/nature13949 · Cited by 428 · see citing works
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Ali, I., Conrad, R. J., Verdin, E. M., & Ott, M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00181 · Cited by 366 · see citing works
Li, X. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms108 · Cited by 360 · see citing works
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Sathyanarayan, A., Mashek, M. T., & Mashek, D. G. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.026 · Cited by 360 · see citing works
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Aging and disease: connections to sirtuins
Dönmez, G., & Guarente, L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00548.x · Cited by 312 · see citing works
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Schug, T. T., & Li, X. (2011) · Annals of Medicine · doi:10.3109/07853890.2010.547211 · Cited by 292 · see citing works
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Springer, M., & Moco, S. (2019) · Nutrients · doi:10.3390/nu11010143 · Cited by 293 · see citing works
Nakagawa, T., & Guarente, L. (2011) · Journal of Cell Science · doi:10.1242/jcs.081067 · Cited by 289 · see citing works
Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease
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Lee, J., Padhye, A., Sharma, A., Song, G., Miao, J., Mo, Y.-Y., Wang, L., & Kemper, J. K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.094524 · Cited by 259 · see citing works
Self-citationPolyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review
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Hong, S., Moreno‐Navarrete, J. M., Wei, X., Kikukawa, Y., Tzameli, I., Prasad, D., Lee, Y., Asara, J. M., Fernández‐Real, J. M., Maratos–Flier, E., et al. (2015) · Nature Medicine · doi:10.1038/nm.3882 · Cited by 258 · see citing works
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Choi, S., Fu, T., Seok, S., Kim, D., Yu, E., Lee, K. W., KANG, Y. Y., Li, X., KEMPER, B. W., & Kemper, J. K. (2013) · Aging Cell · doi:10.1111/acel.12135 · Cited by 245 · see citing works
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Byun, S., Seok, S., Kim, Y., Zhang, Y., Yau, P. M., Iwamori, N., Xu, H. E., Ma, J., KEMPER, B. W., & Kemper, J. K. (2020) · Nature Communications · doi:10.1038/s41467-020-14384-z · Cited by 220 · see citing works
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Fu, T., Seok, S., Choi, S.-E., Huang, Z., Suino-Powell, K., Xu, H., Kemper, B., & Kemper, J. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00596-14 · Cited by 187 · see citing works
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Fu, T., Choi, S.-E., Kim, D.-H., Seok, S., Suino-Powell, K., Xu, H., & Kemper, J. (2012) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1205951109 · Cited by 143 · see citing works
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Martínez‐Redondo, P., & Vaquero, A. (2013) · Genes & Cancer · doi:10.1177/1947601913483767 · Cited by 142 · see citing works
Bile Acid-Activated Receptors: A Review on FXR and Other Nuclear Receptors
Shin, D., & Wang, L. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_236 · Cited by 141 · see citing works
Cellular and molecular effects of sirtuins in health and disease
Horio, Y., Hayashi, T., Kuno, A., & Kunimoto, R. (2011) · Clinical Science · doi:10.1042/cs20100587 · Cited by 137 · see citing works
Wu, T., Liu, Y., Fu, Y., Liu, X., & Zhou, X.-H. (2014) · PubMed · Cited by 135 · see citing works
García‐Rodríguez, J. L., Barbier‐Torres, L., Fernández-Álvarez, S., Juan, V. G., Monte, M. J., Halilbasic, E., Herranz, D., Álvarez, L., Aspichueta, P., Marı́n, J. J. G., et al. (2013) · Hepatology · doi:10.1002/hep.26971 · Cited by 128 · see citing works
miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression
Hanin, G., Yayon, N., Tzur, Y. B., Haviv, R., Bennett, E. R., Udi, S., Krishnamoorthy, Y., Kotsiliti, E., Zangen, R., Efron, B., et al. (2017) · Gut · doi:10.1136/gutjnl-2016-312869 · Cited by 120 · see citing works
A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity
Kim, D., Xiao, Z., Kwon, S., Sun, X., Ryerson, D., Tkac, D., Ma, P., Wu, S., Chiang, C., Zhou, E., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201489527 · Cited by 126 · see citing works
Self-citationSIRT1 metabolic actions: Integrating recent advances from mouse models
Boutant, M., & Cantó, C. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.10.006 · Cited by 121 · see citing works
The Current State of NAD+‐Dependent Histone Deacetylases (Sirtuins) as Novel Therapeutic Targets
Schiedel, M., Robaa, D., Rumpf, T., Sippl, W., & Jung, M. (2017) · Medicinal Research Reviews · doi:10.1002/med.21436 · Cited by 122 · see citing works
Tapia‐Hernández, J. A., Rodríguez‐Félix, F., Juárez, J., Ruíz‐Cruz, S., Robles-García, M. Á., Borboa‐Flores, J., Wong‐Corral, F. J., Cinco-Moroyoqui, F. J., Castro‐Enríquez, D. D., & Del‐Toro‐Sánchez, C. L. (2018) · Food Research International · doi:10.1016/j.foodres.2018.05.036 · Cited by 119 · see citing works
Wu, W., Zhu, B., Peng, X., Zhou, M.-L., Jia, D., & Gu, J.-X. (2014) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2013.11.057 · Cited by 111 · see citing works
Farnesoid X receptor: A “homeostat” for hepatic nutrient metabolism
Massafra, V., & van Mil, S. W. C. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.10.003 · Cited by 113 · see citing works
Nrf2 Inhibits LXRα-Dependent Hepatic Lipogenesis by Competing with FXR for Acetylase Binding
Kay, H. Y., Kim, W., Hwang, S. J., Choi, H., Gilroy, R. K., Wan, Y. Y., & Kim, S. G. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3834 · Cited by 113 · see citing works
Controlling SIRT1 expression by microRNAs in health and metabolic disease
Lee, J., & Kemper, J. K. (2010) · Aging · doi:10.18632/aging.100184 · Cited by 111 · see citing works
Self-citationAnti-inflammatory and metabolic actions of FXR: Insights into molecular mechanisms
Hollman, D. A. A., Milona, A., van Erpecum, K. J., & van Mil, S. W. C. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.07.004 · Cited by 108 · see citing works
Kemper, J. K. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.11.011 · Cited by 108 · see citing works
Self-citationNuclear bile acid signaling through the farnesoid X receptor
Mazuy, C., Helleboid, A., Staels, B., & Lefebvre, P. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1805-y · Cited by 111 · see citing works
The Role and Mechanism of Oxidative Stress and Nuclear Receptors in the Development of NAFLD
Hong, T., Chen, Y., Li, X., & Lü, Y. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6889533 · Cited by 104 · see citing works
Kwon, S., Seok, S., Yau, P. M., Li, X., KEMPER, B. W., & Kemper, J. K. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.778720 · Cited by 102 · see citing works
Self-citationTissue-specific function of farnesoid X receptor in liver and intestine
Zhu, Y., Li, F., & Guo, G. L. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2010.12.018 · Cited by 101 · see citing works
Yin Yang 1 promotes hepatic steatosis through repression of farnesoid X receptor in obese mice
Lu, Y., Ma, Z., Zhang, Z., Xiong, X., Wang, X., Zhang, H., Shi, G., Xia, X., Ning, G., & Li, X. (2013) · Gut · doi:10.1136/gutjnl-2012-303150 · Cited by 100 · see citing works
Bile acids and colon cancer: Is FXR the solution of the conundrum?
Gadaleta, R. M., García‐Irigoyen, O., & Moschetta, A. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.002 · Cited by 99 · see citing works
Hepatic glucose sensing and integrative pathways in the liver
Oosterveer, M. H., & Schoonjans, K. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1505-z · Cited by 96 · see citing works
Role of FXR in Liver Inflammation during Nonalcoholic Steatohepatitis
Armstrong, L. E., & Guo, G. L. (2017) · Current Pharmacology Reports · doi:10.1007/s40495-017-0085-2 · Cited by 91 · see citing works
Sirt1 deacetylates c-Myc and promotes c-Myc/Max association
Mao, B., Zhao, G., Lv, X., Chen, H., Xue, Z., Yang, B., Liu, D., & Liang, C. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.07.006 · Cited by 92 · see citing works
Role of miRNAs in the pathogenesis and susceptibility of diabetes mellitus
Hashimoto, N., & Tanaka, T. (2016) · Journal of Human Genetics · doi:10.1038/jhg.2016.150 · Cited by 90 · see citing works
Purushotham, A., Xu, Q., Lu, J., Foley, J. F., Yan, X., Kim, D.-H., Kemper, J. K., & Li, X. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.05988-11 · Cited by 87 · see citing works
Self-citationCurrent trends in protein acetylation analysis
Diallo, I., Seve, M., Cunin, V., Minassian, F., Poisson, J., Michelland, S., & Bourgoin‐Voillard, S. (2018) · Expert Review of Proteomics · doi:10.1080/14789450.2019.1559061 · Cited by 91 · see citing works
Kuno, A., Hori, Y. S., Hosoda, R., Tanno, M., Miura, T., Shimamoto, K., & Horio, Y. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.392050 · Cited by 88 · see citing works
Dollerup, O. L., Trammell, S. A. J., Hartmann, B., Holst, J. J., Christensen, B., Møller, N., Gillum, M. P., Treebak, J. T., & Jessen, N. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-01081 · Cited by 77 · see citing works
Recent advances on FXR-targeting therapeutics
Panzitt, K., Zollner, G., Marschall, H., & Wagner, M. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111678 · Cited by 86 · see citing works
Xu, W., Cui, C., Cui, C., Chen, Z., Zhang, H., Cui, Q., Xu, G., Fan, J., Han, Y., Tang, L., et al. (2022) · Hepatology · doi:10.1002/hep.32577 · Cited by 86 · see citing works
Regulation of SIRT1 by MicroRNAs
Choi, S., & Kemper, J. K. (2013) · Molecules and Cells · doi:10.1007/s10059-013-0297-1 · Cited by 86 · see citing works
Self-citationPaxton, J. W. (2012) · InTech eBooks · doi:10.5772/1180 · Cited by 88 · see citing works
SIRT1 Regulation in Ageing and Obesity
Pardo, P. S., & Boriek, A. M. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111249 · Cited by 90 · see citing works
Role of Sirtuin 1 in the Regulation of Hepatic Gene Expression by Thyroid Hormone
Thakran, S., Sharma, P., Attia, R. R., Hori, R. T., Deng, X., Elam, M. B., & Park, E. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.437970 · Cited by 84 · see citing works
Bile Acids, Their Receptors, and the Gut Microbiota
Poland, J. C., & Flynn, C. R. (2021) · Physiology · doi:10.1152/physiol.00028.2020 · Cited by 85 · see citing works
Kidney aging—inevitable or preventable?
Choudhury, D., & Levi, M. (2011) · Nature Reviews Nephrology · doi:10.1038/nrneph.2011.104 · Cited by 83 · see citing works
Sirtuin 1: A Target for Kidney Diseases
Kong, L., Wu, H., Zhou, W., Luo, M., Tan, Y., Miao, L., & Cai, L. (2015) · Molecular Medicine · doi:10.2119/molmed.2014.00211 · Cited by 82 · see citing works
Acute exercise activates AMPK and eNOS in the mouse aorta
Cacicedo, J. M., Gauthier, M., LeBrasseur, N. K., Jasuja, R., Ruderman, N. B., & Ido, Y. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01279.2010 · Cited by 81 · see citing works
Wang, T., Zhou, Z., Sun, L., Li, X., Xu, Z., Mi, C., Zhao, G., Jiang, Z., & Zhang, L. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2014.119 · Cited by 80 · see citing works
Histone and Non-Histone Targets of Dietary Deacetylase Inhibitors
Kim, E., Bisson, W. H., Löhr, C. V., Williams, D. E., Ho, E., Dashwood, R. H., & Rajendran, P. (2015) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026615666150825125857 · Cited by 80 · see citing works
Mechanism of Hydrophobic Bile Acid-Induced Hepatocyte Injury and Drug Discovery
Wei, S., Ma, X., & Zhao, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01084 · Cited by 79 · see citing works
- 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
- Health Sciences › Medicine › Surgery › 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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