Endocrine protection of ischemic myocardium by FGF21 from the liver and adipose tissue

Shu Q. Liu; Derek Roberts; Alexei Kharitonenkov; Brian Zhang; Samuel M. Hanson; Yan Chun Li; Li Qun Zhang; Yu H. Wu

doi:10.1038/srep02767

Endocrine protection of ischemic myocardium by FGF21 from the liver and adipose tissue

Shu Q. Liu^*, Derek Roberts, Alexei Kharitonenkov, Brian Zhang, Samuel M. Hanson, Yan Chun Li, Li Qun Zhang, Yu H. Wu

^*Corresponding author for this work

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Abstract

Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective processes, enhancing myocardial tolerance to ischemia. Such processes are present in not only the heart, but also remote organs. In this investigation, we demonstrated a cardioprotective process involving FGF21 from the liver and adipose tissue. In response to myocardial ischemia/reperfusion injury in the mouse, FGF21 was upregulated and released from the hepatic cells and adipocytes into the circulation and interacted with FGFR1 in cardiomyocytes under the mediation of the cell membrane protein β-Klotho, inducing FGFR1 phosphorylation. This action caused phosphorylation of the signaling molecules PI3K p85, Akt1, and BAD, thereby reducing caspase 3 activity, cell death, and myocardial infarction in association with improvement of myocardial function. These observations suggest that FGF21 is upregulated and released from the liver and adipose tissue in myocardial injury, contributing to myocardial protection by the mediation of the FGFR1/β-Klotho-PI3K-Akt1-BAD signaling network.

Original language	English (US)
Article number	2767
Journal	Scientific reports
Volume	3
DOIs	https://doi.org/10.1038/srep02767
State	Published - 2013

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@article{656cd73ce8de4abeac90e47e324a70d5,

title = "Endocrine protection of ischemic myocardium by FGF21 from the liver and adipose tissue",

abstract = "Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective processes, enhancing myocardial tolerance to ischemia. Such processes are present in not only the heart, but also remote organs. In this investigation, we demonstrated a cardioprotective process involving FGF21 from the liver and adipose tissue. In response to myocardial ischemia/reperfusion injury in the mouse, FGF21 was upregulated and released from the hepatic cells and adipocytes into the circulation and interacted with FGFR1 in cardiomyocytes under the mediation of the cell membrane protein β-Klotho, inducing FGFR1 phosphorylation. This action caused phosphorylation of the signaling molecules PI3K p85, Akt1, and BAD, thereby reducing caspase 3 activity, cell death, and myocardial infarction in association with improvement of myocardial function. These observations suggest that FGF21 is upregulated and released from the liver and adipose tissue in myocardial injury, contributing to myocardial protection by the mediation of the FGFR1/β-Klotho-PI3K-Akt1-BAD signaling network.",

author = "Liu, {Shu Q.} and Derek Roberts and Alexei Kharitonenkov and Brian Zhang and Hanson, {Samuel M.} and Li, {Yan Chun} and Zhang, {Li Qun} and Wu, {Yu H.}",

note = "Funding Information: This research was supported by the National Science Foundation.",

year = "2013",

doi = "10.1038/srep02767",

language = "English (US)",

volume = "3",

journal = "Scientific Reports",

issn = "2045-2322",

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T1 - Endocrine protection of ischemic myocardium by FGF21 from the liver and adipose tissue

AU - Liu, Shu Q.

AU - Roberts, Derek

AU - Kharitonenkov, Alexei

AU - Zhang, Brian

AU - Hanson, Samuel M.

AU - Li, Yan Chun

AU - Zhang, Li Qun

AU - Wu, Yu H.

N1 - Funding Information: This research was supported by the National Science Foundation.

PY - 2013

Y1 - 2013

N2 - Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective processes, enhancing myocardial tolerance to ischemia. Such processes are present in not only the heart, but also remote organs. In this investigation, we demonstrated a cardioprotective process involving FGF21 from the liver and adipose tissue. In response to myocardial ischemia/reperfusion injury in the mouse, FGF21 was upregulated and released from the hepatic cells and adipocytes into the circulation and interacted with FGFR1 in cardiomyocytes under the mediation of the cell membrane protein β-Klotho, inducing FGFR1 phosphorylation. This action caused phosphorylation of the signaling molecules PI3K p85, Akt1, and BAD, thereby reducing caspase 3 activity, cell death, and myocardial infarction in association with improvement of myocardial function. These observations suggest that FGF21 is upregulated and released from the liver and adipose tissue in myocardial injury, contributing to myocardial protection by the mediation of the FGFR1/β-Klotho-PI3K-Akt1-BAD signaling network.

AB - Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective processes, enhancing myocardial tolerance to ischemia. Such processes are present in not only the heart, but also remote organs. In this investigation, we demonstrated a cardioprotective process involving FGF21 from the liver and adipose tissue. In response to myocardial ischemia/reperfusion injury in the mouse, FGF21 was upregulated and released from the hepatic cells and adipocytes into the circulation and interacted with FGFR1 in cardiomyocytes under the mediation of the cell membrane protein β-Klotho, inducing FGFR1 phosphorylation. This action caused phosphorylation of the signaling molecules PI3K p85, Akt1, and BAD, thereby reducing caspase 3 activity, cell death, and myocardial infarction in association with improvement of myocardial function. These observations suggest that FGF21 is upregulated and released from the liver and adipose tissue in myocardial injury, contributing to myocardial protection by the mediation of the FGFR1/β-Klotho-PI3K-Akt1-BAD signaling network.

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JO - Scientific Reports

JF - Scientific Reports

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ER -

Endocrine protection of ischemic myocardium by FGF21 from the liver and adipose tissue

Abstract

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