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 journalArticle

1 Citation (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 languageEnglish
Article number37196
Pages (from-to)1825-1831
Number of pages7
JournalFEBS Letters
Volume589
Issue number15
DOIs
Publication statusPublished - 2015 Jul 3

Fingerprint

Obese Mice
High Fat Diet
Nutrition
Interleukin-6
Fats
Liver
Neurodegenerative diseases
RNA Precursors
DNA-Binding Proteins
Processing
Neurodegenerative Diseases
Adipose Tissue
Homeostasis
Obesity
RNA
Tissue
Feedback
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Lee, Sungwook ; Lee, Taeyun A. ; Song, Su Jin ; Park, Taesun ; Park, Boyoun. / Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice. In: FEBS Letters. 2015 ; Vol. 589, No. 15. pp. 1825-1831.
@article{5d889d12b32645119d366c8e7b711b6a,
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",
year = "2015",
month = "7",
day = "3",
doi = "10.1016/j.febslet.2015.05.040",
language = "English",
volume = "589",
pages = "1825--1831",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "15",

}

Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice. / Lee, Sungwook; Lee, Taeyun A.; Song, Su Jin; Park, Taesun; Park, Boyoun.

In: FEBS Letters, Vol. 589, No. 15, 37196, 03.07.2015, p. 1825-1831.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice

AU - Lee, Sungwook

AU - Lee, Taeyun A.

AU - Song, Su Jin

AU - Park, Taesun

AU - Park, Boyoun

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.

UR - http://www.scopus.com/inward/record.url?scp=84934436963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84934436963&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2015.05.040

DO - 10.1016/j.febslet.2015.05.040

M3 - Article

C2 - 26037142

AN - SCOPUS:84934436963

VL - 589

SP - 1825

EP - 1831

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 15

M1 - 37196

ER -