Cited by 431Fibroblast Growth Factor ResearchMetabolism, Diabetes, and CancerPancreatic function and diabetes

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FGF15/19 Regulates Hepatic Glucose Metabolism by Inhibiting the CREB-PGC-1α Pathway

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Potthoff, Matthew J., Boney-Montoya, Jamie, Choi, Mihwa, He, Tianteng, Sunny, Nishanth E., Satapati, Santhosh, Suino-Powell, Kelly, Xu, H. Eric, Gerard, Robert D., Finck, Brian N., Burgess, Shawn C., Mangelsdorf, David J., Kliewer, Steven A.·2011·Cell Metabolism

DOI 10.1016/j.cmet.2011.03.019PMC PMC3131185

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Abstract

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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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: Potthoff, Matthew J.
Choi, Mihwa
Sunny, Nishanth E.
Satapati, Santhosh
Xu, H. Eric
Finck, Brian N.
Burgess, Shawn C.
Mangelsdorf, David J.
Kliewer, Steven A.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2011-06
Volume: 13
Issue: 6
Pages: 729-738
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2011.03.019
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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FGF15/19 Regulates Hepatic Glucose Metabolism by Inhibiting the CREB-PGC-1α Pathway

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