Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice

Sungwook Lee; Taeyun A. Lee; Su Jin Song; Taesun Park; Boyoun Park

doi:10.1016/j.febslet.2015.05.040

Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice

Sungwook Lee, Taeyun A. Lee, Su Jin Song, Taesun Park, Boyoun Park

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Abstract Inclusion of Tat-activating regulatory DNA-binding protein-43 (TDP-43) due to hyperphosphorylation or hyperubiquitination is a cause of neurodegenerative disease. Cellular TDP-43 expression is tightly controlled through a negative feedback loop involving its mRNA. Recently, we reported that the TDP-43-mediated sub-nuclear body is an essential site of interleukin-6 (IL-6) pre-mRNA processing. Here we show that mice fed on a high-fat diet exhibit increased TDP-43 expression in the liver and adipose tissue with a prominent increase in IL-6. TDP-43 depletion in vivo reduces IL-6 production in the liver. Overexpression or depletion of TDP-43 in pre-adipose and adipose cells causes reciprocal alteration of IL-6 expression and RNA processing. Our findings provide evidence for a link between homeostasis of TDP-43 expression and the risk of developing obesity.

Original language	English
Article number	37196
Pages (from-to)	1825-1831
Number of pages	7
Journal	FEBS Letters
Volume	589
Issue number	15
DOIs	https://doi.org/10.1016/j.febslet.2015.05.040
Publication status	Published - 2015 Jul 3

Bibliographical note

Funding Information:
This study was supported by Grants from Basic Science Research Program through the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1220060), and from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C2542). S.L. was supported by the Yonsei University Research Fund of 2014 (2014-12-0135). T.A.L. was supported by Brain Korea (BK21) PLUS Program.

Publisher Copyright:
© 2015 Federation of European Biochemical Societies.

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.febslet.2015.05.040

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title = "Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice",

abstract = "Abstract Inclusion of Tat-activating regulatory DNA-binding protein-43 (TDP-43) due to hyperphosphorylation or hyperubiquitination is a cause of neurodegenerative disease. Cellular TDP-43 expression is tightly controlled through a negative feedback loop involving its mRNA. Recently, we reported that the TDP-43-mediated sub-nuclear body is an essential site of interleukin-6 (IL-6) pre-mRNA processing. Here we show that mice fed on a high-fat diet exhibit increased TDP-43 expression in the liver and adipose tissue with a prominent increase in IL-6. TDP-43 depletion in vivo reduces IL-6 production in the liver. Overexpression or depletion of TDP-43 in pre-adipose and adipose cells causes reciprocal alteration of IL-6 expression and RNA processing. Our findings provide evidence for a link between homeostasis of TDP-43 expression and the risk of developing obesity.",

author = "Sungwook Lee and Lee, {Taeyun A.} and Song, {Su Jin} and Taesun Park and Boyoun Park",

note = "Funding Information: This study was supported by Grants from Basic Science Research Program through the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1220060), and from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C2542). S.L. was supported by the Yonsei University Research Fund of 2014 (2014-12-0135). T.A.L. was supported by Brain Korea (BK21) PLUS Program. Publisher Copyright: {\textcopyright} 2015 Federation of European Biochemical Societies.",

year = "2015",

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doi = "10.1016/j.febslet.2015.05.040",

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AU - Lee, Sungwook

AU - Lee, Taeyun A.

AU - Song, Su Jin

AU - Park, Taesun

AU - Park, Boyoun

N1 - Funding Information: This study was supported by Grants from Basic Science Research Program through the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1220060), and from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C2542). S.L. was supported by the Yonsei University Research Fund of 2014 (2014-12-0135). T.A.L. was supported by Brain Korea (BK21) PLUS Program. Publisher Copyright: © 2015 Federation of European Biochemical Societies.

PY - 2015/7/3

Y1 - 2015/7/3

N2 - Abstract Inclusion of Tat-activating regulatory DNA-binding protein-43 (TDP-43) due to hyperphosphorylation or hyperubiquitination is a cause of neurodegenerative disease. Cellular TDP-43 expression is tightly controlled through a negative feedback loop involving its mRNA. Recently, we reported that the TDP-43-mediated sub-nuclear body is an essential site of interleukin-6 (IL-6) pre-mRNA processing. Here we show that mice fed on a high-fat diet exhibit increased TDP-43 expression in the liver and adipose tissue with a prominent increase in IL-6. TDP-43 depletion in vivo reduces IL-6 production in the liver. Overexpression or depletion of TDP-43 in pre-adipose and adipose cells causes reciprocal alteration of IL-6 expression and RNA processing. Our findings provide evidence for a link between homeostasis of TDP-43 expression and the risk of developing obesity.

AB - Abstract Inclusion of Tat-activating regulatory DNA-binding protein-43 (TDP-43) due to hyperphosphorylation or hyperubiquitination is a cause of neurodegenerative disease. Cellular TDP-43 expression is tightly controlled through a negative feedback loop involving its mRNA. Recently, we reported that the TDP-43-mediated sub-nuclear body is an essential site of interleukin-6 (IL-6) pre-mRNA processing. Here we show that mice fed on a high-fat diet exhibit increased TDP-43 expression in the liver and adipose tissue with a prominent increase in IL-6. TDP-43 depletion in vivo reduces IL-6 production in the liver. Overexpression or depletion of TDP-43 in pre-adipose and adipose cells causes reciprocal alteration of IL-6 expression and RNA processing. Our findings provide evidence for a link between homeostasis of TDP-43 expression and the risk of developing obesity.

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Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice

Abstract

Bibliographical note

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UN SDGs

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