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 journalArticlepeer-review

7 Citations (Scopus)


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
Issue number15
Publication statusPublished - 2015 Jul 3

Bibliographical note

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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