Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21
Open accessAbstract
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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Fgf21 causes resistance to growth hormone.
“Given the observation that Fgf21 causes resistance to GH (Inagaki et al, 2008)”
From Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency (2018) · cites this paper as Inagaki et al, 2008
High plasma FGF21 reduces growth hormone signaling, resulting in a marked growth defect.
“Given that high plasma concentrations of FGF21 have been observed to reduce growth hormone signaling, resulting in a marked growth defect (Inagaki et al, 2008)”
From Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency (2018) · cites this paper as Inagaki et al, 2008
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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.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 8
- Issue
- 1
- Pages
- 77-83
- ISSN
- 1550-4131 (ISSN-L)
- 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
- 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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