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Hyperproduction of IL-6 caused by aberrant TDP-43 overexpression in high-fat diet-induced obese mice
作者:, Boyoun Park
摘要: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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发表期刊:FEBS Letters Volume 589, Issue 15
发表时间:Wed Jul 08 00:00:00 CST 2015
数字识别码:10.1016/j.febslet.2015.05.040
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