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

Takeshi Inagaki; Vicky Y. Lin; Regina Goetz; Moosa Mohammadi; David J. Mangelsdorf; Steven A. Kliewer

doi:10.1016/j.cmet.2008.05.006

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

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

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341 Scopus citations

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.

Original language	English (US)
Pages (from-to)	77-83
Number of pages	7
Journal	Cell Metabolism
Volume	8
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2008.05.006
State	Published - Jul 2 2008

Keywords

HUMDISEASE
SIGNALING

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2008.05.006

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title = "Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21",

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.",

keywords = "HUMDISEASE, SIGNALING",

author = "Takeshi Inagaki and Lin, {Vicky Y.} and Regina Goetz and Moosa Mohammadi and Mangelsdorf, {David J.} and Kliewer, {Steven A.}",

note = "Funding Information: We thank Norma Anderson for assistance with the metabolic cages, Dr. James Richardson and John Shelton for histology and photography, members of the Kliewer/Mangelsdorf laboratory for technical assistance, and Dr. Peter Rotwein for comments on the manuscript. This work was supported by National Institutes of Health grants 1RL1GM084436-01 and 1PL1DK081182-01 (D.J.M. and S.A.K.), and DE13686 (M.M.), the Welch Foundation (D.J.M. and S.A.K.), and the Howard Hughes Medical Institute (V.Y.L. and D.J.M.). D.J.M. is an investigator of the Howard Hughes Medical Institute. ",

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AU - Mohammadi, Moosa

AU - Mangelsdorf, David J.

AU - Kliewer, Steven A.

N1 - Funding Information: We thank Norma Anderson for assistance with the metabolic cages, Dr. James Richardson and John Shelton for histology and photography, members of the Kliewer/Mangelsdorf laboratory for technical assistance, and Dr. Peter Rotwein for comments on the manuscript. This work was supported by National Institutes of Health grants 1RL1GM084436-01 and 1PL1DK081182-01 (D.J.M. and S.A.K.), and DE13686 (M.M.), the Welch Foundation (D.J.M. and S.A.K.), and the Howard Hughes Medical Institute (V.Y.L. and D.J.M.). D.J.M. is an investigator of the Howard Hughes Medical Institute.

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N2 - 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.

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

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