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FGF15/19 Regulates Hepatic Glucose Metabolism by Inhibiting the CREB-PGC-1α Pathway
Open accessAbstract
Regulation of hepatic carbohydrate homeostasis is crucial for maintaining energy balance in the face of fluctuating nutrient availability. Here, we show that the hormone fibroblast growth factor 15/19 (FGF15/19), which is released postprandially from the small intestine, inhibits hepatic gluconeogenesis, like insulin. However, unlike insulin, which peaks in serum 15 min after feeding, FGF15/19 expression peaks approximately 45 min later, when bile acid concentrations increase in the small intestine. FGF15/19 blocks the expression of genes involved in gluconeogenesis through a mechanism involving the dephosphorylation and inactivation of the transcription factor cAMP regulatory element-binding protein (CREB). This in turn blunts expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and other genes involved in hepatic metabolism. Overexpression of PGC-1α blocks the inhibitory effect of FGF15/19 on gluconeogenic gene expression. These results demonstrate that FGF15/19 works subsequent to insulin as a postprandial regulator of hepatic carbohydrate homeostasis.
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“It is recognized that intestine‐secreted FGF15 also plays a pivotal role in the regulation of energy metabolism and liver cell regeneration (Potthoff et al., 2011).”
From Akkermansia muciniphila alleviates high‐fat‐diet ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Potthoff et al., 2011
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“FGF19 also increases liver protein and glycogen synthesis while repressing hepatic glucose production 43, 44, in order to ensure proper postprandial energy storage independently from insulin.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [44]
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Cites
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
Transcriptional regulation by the phosphorylation-dependent factor CREB
Mayr, B., & Montminy, M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35085068 · Cited by 2,587
Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133
Gonzalez, G. A., & Montminy, M. (1989) · Cell · doi:10.1016/0092-8674(89)90013-5 · Cited by 2,464
Puigserver, P., & Spiegelman, B. M. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0012 · Cited by 2,076
Phosphorylated CREB binds specifically to the nuclear protein CBP
Chrivia, J. C., Kwok, R. P. S., Lamb, N., Hagiwara, M., Montminy, M. R., & Goodman, R. H. (1993) · Nature · doi:10.1038/365855a0 · Cited by 2,052
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865
Self-citationInagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504
Self-citationPGC-1 coactivators: inducible regulators of energy metabolism in health and disease
Finck, B. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27794 · Cited by 1,461
Self-citationNuclear protein CBP is a coactivator for the transcription factor CREB
Kwok, R. P. S., Lundblad, J. R., Chrivia, J. C., Richards, J. P., Bächinger, H. P., Brennan, R. G., Roberts, S. G. E., Green, M. R., & Goodman, R. H. (1994) · Nature · doi:10.1038/370223a0 · Cited by 1,443
CREB regulates hepatic gluconeogenesis through the coactivator PGC-1
Herzig, S., Long, F., Jhala, U. S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schutz, G., Yoon, C., Puigserver, P., et al. (2001) · Nature · doi:10.1038/35093131 · Cited by 1,440
Peroxisome proliferator–activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis
Lehman, J. J., Barger, P. M., Kovacs, A., Saffitz, J. E., Medeiros, D. M., & Kelly, D. P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10268 · Cited by 1,285
Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice
Lin, J., Wu, P.-H., Tarr, P. T., Lindenberg, K. S., St-Pierre, J., Zhang, C.-Y., Mootha, V. K., Jäger, S., Vianna, C. R., Reznick, R. M., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.013 · Cited by 1,162
Handschin, C., & Spiegelman, B. M. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0037 · Cited by 1,090
The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism
Koo, S., Flechner, L., Qi, L., Zhang, X., Screaton, R. A., Jeffries, S., Hedrick, S. A., Xu, W., Boussouar, F., Brindle, P. K., et al. (2005) · Nature · doi:10.1038/nature03967 · Cited by 1,026
Kurosu, H., Choi, M., Ogawa, Y., Dickson, A. S., Goetz, R., Eliseenkova, A. V., Mohammadi, M., Rosenblatt, K. P., Kliewer, S. A., & Kuro-o, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704165200 · Cited by 748
Self-citationAyala, J. E., Samuel, V. T., Morton, G. J., Obici, S., Croniger, C. M., Shulman, G. I., Wasserman, D. H., & McGuinness, O. P. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.006239 · Cited by 722
Holt, J. A., Luo, G., Billin, A. N., Bisi, J., McNeill, Y. Y., Kozarsky, K., Donahee, M. H., Wang, D. Y., Mansfield, T. A., Kliewer, S. A., et al. (2003) · Genes & Development · doi:10.1101/gad.1083503 · Cited by 714
Self-citationThe CREB Coactivator TORC2 Functions as a Calcium- and cAMP-Sensitive Coincidence Detector
Screaton, R. A., Conkright, M. D., Katoh, Y., Best, J. L., Canettieri, G., Jeffries, S., Guzmán, E., Niessen, S., Yates, J. R., Takemori, H., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.015 · Cited by 654
FGF19 as a Postprandial, Insulin-Independent Activator of Hepatic Protein and Glycogen Synthesis
Kir, S., Beddow, S. A., Samuel, V. T., Miller, P., Previs, S. F., Suino-Powell, K., Xu, H. E., Shulman, G. I., Kliewer, S. A., & Mangelsdorf, D. J. (2011) · Science · doi:10.1126/science.1198363 · Cited by 637
Self-citationFu, L., John, L. M., Adams, S. H., Yu, X. X., Tomlinson, E., Renz, M. E., Williams, P. M., Soriano, R. H., Corpuz, R. T., Moffat, B., et al. (2004) · Endocrinology · doi:10.1210/en.2003-1671 · Cited by 584
Tomlinson, E., Fu, L., John, L., Hultgren, B., Huang, X., Renz, M., Stephan, J. P., Tsai, S. P., Powell-Braxton, L., French, D., et al. (2002) · Endocrinology · doi:10.1210/endo.143.5.8850 · Cited by 576
Goetz, R. M., Beenken, A., Ibrahimi, O. A., Kalinina, J., Olsen, S. K., Eliseenkova, A. V., Xu, C.-F., Neubert, T. A., Zhang, F., Linhardt, R. J., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02249-06 · Cited by 550
Self-citationHagiwara, M., Alberts, A. S., Brindle, P. K., Meinkoth, J. L., Feramisco, J. R., Deng, T., Karin, M., Shenolikar, S., & Montminy, M. (1992) · Cell · doi:10.1016/0092-8674(92)90537-m · Cited by 457
Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2
Dentin, R., Liu, Y., Koo, S., Hedrick, S. A., Vargas, T., Heredia, J., Yates, J. R., & Montminy, M. (2007) · Nature · doi:10.1038/nature06128 · Cited by 407
Considerations in the Design of Hyperinsulinemic-Euglycemic Clamps in the Conscious Mouse
Ayala, J. E., Bracy, D. P., McGuinness, O. P., & Wasserman, D. H. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-0686 · Cited by 406
Lundåsen, T., Gälman, C., Angelin, B., & Rudling, M. J. (2006) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01731.x · Cited by 403
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
Yu, C., Wang, F., Kan, M., Jin, C., Jones, R. B., Weinstein, M. B., Deng, C., & McKeehan, W. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.20.15482 · Cited by 348
A New Mechanism for Bile Acid Diarrhea: Defective Feedback Inhibition of Bile Acid Biosynthesis
Walters, J. R. F., Tasleem, A. M., Omer, O. S., Brydon, W. G., Dew, T. K., & le Roux, C. W. (2009) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.04.024 · Cited by 318
Wadzinski, B. E., Wheat, W. H., Jaspers, S. R., Peruski, L. F., Lickteig, R. L., Johnson, G. L., & Klemm, D. J. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.5.2822 · Cited by 303
Identification of a hormonal basis for gallbladder filling
Choi, M., Moschetta, A., Bookout, A. L., Peng, L., Umetani, M., Holmstrom, S. R., Suino-Powell, K. M., Xu, H. E., Richardson, J. A., Gerard, R. D., et al. (2006) · Nature Medicine · doi:10.1038/nm1501 · Cited by 290
Self-citationLiver-specific Activities of FGF19 Require Klotho beta
Lin, B. C., Wang, M., Blackmore, C. A., & Desnoyers, L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704244200 · Cited by 288
Burgess, S. C., He, T.-T., Yan, Z., Lindner, J., Sherry, A. D., Malloy, C. R., Browning, J. D., & Magnuson, M. A. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.03.004 · Cited by 276
Self-citationBittinger, M. A., McWhinnie, E. A., Meltzer, J., Iourgenko, V., Latario, B., Liu, X., Chen, C. H., Song, C., Garza, D., & Labow, M. (2004) · Current Biology · doi:10.1016/j.cub.2004.11.002 · Cited by 235
Fibroblast Growth Factor-19, a Novel Factor That Inhibits Hepatic Fatty Acid Synthesis
Bhatnagar, S., Damron, H. A., & Hillgartner, F. B. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808818200 · Cited by 212
The multifunctional role of the co-activator CBP in transcriptional regulation.
Goldman, P. S., Tran, V. K., & Goodman, R. H. (1997) · PubMed · Cited by 196
Glycemic Control in Mice with Targeted Disruption of the Glucagon Receptor Gene
Parker, J. C., Andrews, K. M., Allen, M. R., Stock, J. L., & McNeish, J. D. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.6265 · Cited by 160
In vivo insulin sensitivity in the rat determined by euglycemic clamp
Kraegen, E. W., James, D. E., Bennett, S. P., & Chisholm, D. J. (1983) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1983.245.1.e1 · Cited by 153
Wright, T. J., Ladher, R., Mcwhirter, J., Murre, C., Schoenwolf, G., & Mansour, S. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.02.003 · Cited by 144
Co-receptor Requirements for Fibroblast Growth Factor-19 Signaling
Wu, X., Ge, H., Gupte, J., Weiszmann, J., Shimamoto, G., Stevens, J., Hawkins, N., Lemon, B., Shen, W., Xu, J., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700130200 · Cited by 140
FGFR4 Prevents Hyperlipidemia and Insulin Resistance but Underlies High-Fat Diet–Induced Fatty Liver
Huang, X., Yang, C., Luo, Y., Jin, C., Wang, F., & McKeehan, W. L. (2007) · Diabetes · doi:10.2337/db07-0648 · Cited by 137
Burgess, S. C., Leone, T. C., Wende, A. R., Croce, M. A., Chen, Z., Sherry, A. D., Malloy, C. R., & Finck, B. N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600050200 · Cited by 111
Self-citationMichael, L. F., Asahara, H., Shulman, A. I., Kraus, W. L., & Montminy, M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.5.1596-1603.2000 · Cited by 104
Wadzinski, B. E., Wheat, W. H., Jaspers, S. R., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.5.2822-2834.1993 · Cited by 87
Wang, Z., Zhang, B., Wang, M., & Carr, B. I. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209108200 · Cited by 82
Noninvasive evaluation of liver metabolism by 2H and 13C NMR isotopomer analysis of human urine
Burgess, S. C., Weis, B. C., Jones, J. G., Smith, E. M., Merritt, M. E., Margolis, D. M., Sherry, A. D., & Malloy, C. R. (2003) · Analytical Biochemistry · doi:10.1016/s0003-2697(02)00465-7 · Cited by 55
Self-citationStejskal, D., Karpíšek, M., Hanulova, Z., & Stejskal, P. (2008) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365510701854967 · Cited by 49
Fibroblast Growth Factor 19 Serum Levels: Relation to Renal Function and Metabolic Parameters
Reiche, M., Bachmann, A., Lössner, U., Blüher, M., Stümvoll, M., & Faßhauer, M. (2009) · Hormone and Metabolic Research · doi:10.1055/s-0029-1243249 · Cited by 45
Sunny, N. E., & Bequette, B. J. (2009) · Journal of Animal Science · doi:10.2527/jas.2009-2479 · Cited by 28
Self-citationÅhrén, B., & Havel, P. J. (1999) · International Journal of Obesity · doi:10.1038/sj.ijo.0800899 · Cited by 21
Adenoviral targeting of gene expression to tumors
Hogg, R. T., Garcia, J. A., & Gerard, R. D. (2010) · Cancer Gene Therapy · doi:10.1038/cgt.2010.1 · Cited by 13
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Metadata
- Authors
- Potthoff, M. J., Boney-Montoya, J., Choi, M., He, T., Sunny, N. E., Satapati, S., Suino-Powell, K., Xu, H. E., Gerard, R. D., Finck, B. N., Burgess, S. C., Mangelsdorf, D. J., & Kliewer, S. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Van Andel Institute (US)
- Washington University in St. Louis (US)
- Corresponding author
- Mangelsdorf, David J.
- Kliewer, Steven A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 13
- Issue
- 6
- Pages
- 729-738
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3131185
- OpenAlex
- W2020515276
- Cited by
- 431
- References
- 51
- Citations by year
- 2026: 24 · 2025: 28 · 2024: 34 · 2023: 28 · 2022: 47 · 2021: 39 · 2020: 30 · 2019: 25 · 2018: 22 · 2017: 34 · 2016: 18 · 2015: 28 · 2014: 22 · 2013: 20 · 2012: 24
- FWCI
- 9.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 777 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK067158, DK076269, DK078184, DK078187, U19DK62434)
- Howard Hughes Medical Institute
- Welch Foundation (I-1275, I-1588)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- FGF15/19, hepatic gluconeogenesis, CREB, PGC-1α, hepatic glucose metabolism, carbohydrate homeostasis, bile acids, insulin, transcriptional regulation, dephosphorylation
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Citric Acid Cycle, Fatty Acids, Fibroblast Growth Factors, Gluconeogenesis, Glucose, Liver, Luciferases, Male, Mice, Inbred C57BL, Oxidation-Reduction, Transcription Factors, Signal Transduction, Trans-Activators, Gene Expression, Cyclic AMP Response Element-Binding Protein, Genes, Reporter, Mice, Knockout, Gene Expression Profiling, Mice, Metabolic Networks and Pathways
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