FGF21 induces PGC-1α and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response

Matthew J Potthoff; Takeshi Inagaki; Santhosh Satapati; Xunshan Ding; Tianteng He; Regina Goetz; Moosa Mohammadi; Brian N Finck; David J Mangelsdorf; Steven A Kliewer; Shawn C Burgess

doi:10.1073/pnas.0904187106

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FGF21 induces PGC-1α and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response

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FGF21 induces PGC-1α and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response

Matthew J Potthoff, Takeshi Inagaki, Santhosh Satapati, Xunshan Ding, Tianteng He, Regina Goetz, Moosa Mohammadi, Brian N Finck, David J Mangelsdorf, Steven A Kliewer, …

Proceedings of the National Academy of Sciences - PNAS, Vol.106(26), pp.10853-10858

06/30/2009

DOI: 10.1073/pnas.0904187106

PMCID: PMC2705613

PMID: 19541642

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Abstract

The liver plays a crucial role in mobilizing energy during nutritional deprivation. During the early stages of fasting, hepatic glycogenolysis is a primary energy source. As fasting progresses and glycogen stores are depleted, hepatic gluconeogenesis and ketogenesis become major energy sources. Here, we show that fibroblast growth factor 21 (FGF21), a hormone that is induced in liver by fasting, induces hepatic expression of peroxisome proliferator-activated receptor γ coactivator protein-1α (PGC-1α), a key transcriptional regulator of energy homeostasis, and causes corresponding increases in fatty acid oxidation, tricarboxylic acid cycle flux, and gluconeogenesis without increasing glycogenolysis. Mice lacking FGF21 fail to fully induce PGC-1α expression in response to a prolonged fast and have impaired gluconeogenesis and ketogenesis. These results reveal an unexpected relationship between FGF21 and PGC-1α and demonstrate an important role for FGF21 in coordinately regulating carbohydrate and fatty acid metabolism during the progression from fasting to starvation.

Biological Sciences

Lipid Metabolism

liver

glycogenolysis

gluconeogenesis

ketogenesis

Details

Title: Subtitle: FGF21 induces PGC-1α and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response
Creators: Matthew J Potthoff - Department of Pharmacology
Takeshi Inagaki - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390
Santhosh Satapati - Advanced Imaging Center, and
Xunshan Ding - Department of Pharmacology
Tianteng He - Advanced Imaging Center, and
Regina Goetz - Department of Pharmacology, New York University School of Medicine, New York, NY 10016; and
Moosa Mohammadi - Department of Pharmacology, New York University School of Medicine, New York, NY 10016; and
Brian N Finck - Center for Cardiovascular Research and
David J Mangelsdorf - Department of Pharmacology
Steven A Kliewer - Department of Pharmacology
Shawn C Burgess - Department of Pharmacology
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.106(26), pp.10853-10858
DOI: 10.1073/pnas.0904187106
PMID: 19541642
PMCID: PMC2705613
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 06/30/2009
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984040541302771

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