Cited by 409Fibroblast Growth Factor ResearchGrowth Hormone and Insulin-like Growth FactorsLiver physiology and pathology

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Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21

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Inagaki, Takeshi, Lin, Vicky Y., Goetz, Regina, Mohammadi, Moosa, Mangelsdorf, David J., Kliewer, Steven A.·2008·Cell Metabolism

DOI 10.1016/j.cmet.2008.05.006PMC PMC2575072

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Abstract

Starvation blocks the actions of growth hormone (GH) and inhibits growth through mechanisms that are not well understood. In this report, we demonstrate that fibroblast growth factor 21 (FGF21), a hormone induced by fasting, causes GH resistance. In liver, FGF21 reduces concentrations of the active form of signal transducer and activator of transcription 5 (STAT5), a major mediator of GH actions, and causes corresponding decreases in the expression of its target genes, including insulin-like growth factor 1 (IGF-1). FGF21 also induces hepatic expression of IGF-1 binding protein 1 and suppressor of cytokine signaling 2, which blunt GH signaling. Chronic exposure to FGF21 markedly inhibits growth in mice. These data suggest a central role for FGF21 in inhibiting growth as part of its broader role in inducing the adaptive response to starvation.

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Authors: Inagaki, T., Lin, V. Y., Goetz, R., Mohammadi, M., Mangelsdorf, D. J., & Kliewer, S. A.
Affiliations: The University of Texas Southwestern Medical Center (US)
Howard Hughes Medical Institute (US)
New York University (US)
Corresponding author: Kliewer, Steven A.
ORCID: Inagaki, Takeshi
Goetz, Regina
Mohammadi, Moosa
Mangelsdorf, David J.
Kliewer, Steven A.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2008-07
Volume: 8
Issue: 1
Pages: 77-83
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2008.05.006
PMC: PMC2575072
OpenAlex: W2114836473
Cited by: 409
References: 37
Citations by year: 2026: 14 · 2025: 14 · 2024: 22 · 2023: 12 · 2022: 21 · 2021: 35 · 2020: 22 · 2019: 27 · 2018: 22 · 2017: 18 · 2016: 31 · 2015: 44 · 2014: 44 · 2013: 19 · 2012: 26
FWCI: 5.22
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1842 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
National Institute of General Medical Sciences (RL1GM084436)
National Institute of Diabetes and Digestive and Kidney Diseases (PL1DK081182)
National Institute of Dental and Craniofacial Research (DE13686, R01DE013686)
National Center for Research Resources (P20RR020691)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: FGF21, growth hormone signaling, fasting, starvation, growth inhibition, STAT5, insulin-like growth factor I, SOCS2, hepatic gene expression
MeSH terms: Adaptation, Physiological, Animals, Fasting, Fibroblast Growth Factors, Growth, Liver, Growth Hormone, Starvation, Signal Transduction, STAT5 Transcription Factor, Mice

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Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21

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