Lee Sungwook, Lee Taeyun A, Song Su Jin, Park Taesun, Park Boyoun
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul 120-749, South Korea.
FEBS Lett. 2015 Jul 8;589(15):1825-31. doi: 10.1016/j.febslet.2015.05.040. Epub 2015 May 30.
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.
由于过度磷酸化或过度泛素化而包含Tat激活调节性DNA结合蛋白43（TDP-43）是神经退行性疾病的一个病因。细胞中TDP-43的表达通过涉及其mRNA的负反馈回路受到严格控制。最近，我们报道TDP-43介导的亚核体是白细胞介素-6（IL-6）前体mRNA加工的重要位点。在这里，我们表明，喂食高脂饮食的小鼠肝脏和脂肪组织中TDP-43表达增加，IL-6显著增加。体内TDP-43的缺失会降低肝脏中IL-6的产生。在脂肪前体细胞和脂肪细胞中过表达或缺失TDP-43会导致IL-6表达和RNA加工的相互改变。我们的研究结果为TDP-43表达的稳态与肥胖发生风险之间的联系提供了证据。
