Journal article
FGF15/19 Regulates Hepatic Glucose Metabolism by Inhibiting the CREB-PGC-1α Pathway
Cell metabolism, Vol.13(6), pp.729-738
2011
DOI: 10.1016/j.cmet.2011.03.019
PMCID: PMC3131185
PMID: 21641554
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.
► The intestinal hormone, FGF15/19, inhibits postprandial hepatic gluconeogenesis ► FGF15/19 is induced after insulin to regulate postprandial hepatic metabolism ► FGF15/19 suppresses gluconeogenesis by inhibiting the CREB-PGC-1α pathway
Details
- Title: Subtitle
- FGF15/19 Regulates Hepatic Glucose Metabolism by Inhibiting the CREB-PGC-1α Pathway
- Creators
- Matthew J Potthoff - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USAJamie Boney-Montoya - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USAMihwa Choi - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USATianteng He - Advanced Imaging Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USANishanth E Sunny - Advanced Imaging Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USASanthosh Satapati - Advanced Imaging Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USAKelly Suino-Powell - Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USAH. Eric Xu - Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USARobert D Gerard - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USABrian N Finck - Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USAShawn C Burgess - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USADavid J Mangelsdorf - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USASteven A Kliewer - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.13(6), pp.729-738
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cmet.2011.03.019
- PMID
- 21641554
- PMCID
- PMC3131185
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Language
- English
- Date published
- 2011
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984070555002771
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