First Author | Lee S | Year | 2015 |
Journal | FEBS Lett | Volume | 589 |
Issue | 15 | Pages | 1825-31 |
PubMed ID | 26037142 | Mgi Jnum | J:223381 |
Mgi Id | MGI:5648754 | Doi | 10.1016/j.febslet.2015.05.040 |
Citation | Lee S, et al. (2015) Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice. FEBS Lett 589(15):1825-31 |
abstractText | 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. |