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.
Bibliographical noteFunding 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.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology