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

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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

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This output contributes to the following Sustainable Development Goal(s)

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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.",

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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

All Science Journal Classification (ASJC) codes

UN SDGs

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