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 | |
| Publication status | Published - 2015 Jul 3 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology
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}
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 journal › Article
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.
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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 -