Role of Hepatocyte ATF3 in NAFLD

项目摘要 项目摘要：非酒精性脂肪性肝病(NAFLD)是 从单纯性脂肪变性到非酒精性脂肪性肝炎(NASH)。到目前为止， 非酒精性脂肪肝的发病机制尚不清楚。激活转录因子3 (ATF3)是ATF/cAMP反应元件结合(ATF/CREB)转录因子家族的成员， 并抑制巨噬细胞的炎症反应。到目前为止，人们对这一角色一无所知。 肝脏ATF3与脂质代谢的关系我们的初步研究表明，肝脏ATF3的表达是 在普通代谢应激状态下显著降低。ATF3在肝脏中的过度表达可改善血脂 而肝脏ATF3的缺失则有相反的影响。在这个项目中，我们将调查是否和 肝脏ATF3如何调控NAFLD的发生发展我们将同时使用增益函数和损耗函数 完成这一项目的方法。拟议研究的完成可能有助于确定肝细胞ATF3是 脂代谢的关键调节者和NAFLD的发展。

Project Summary Project Summary: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries, which ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). So far, the mechanisms underlying the development of NAFLD is poorly understood. Activating transcription factor 3 (ATF3) is a member of the ATF/cAMP response element-binding (ATF/CREB) family of transcription factors, and inhibits inflammatory response in macrophages. Until now, nothing has been known about the role of hepatic ATF3 in lipid metabolism. Our preliminary studies have shown that hepatic ATF3 expression is markedly reduced under common metabolic stress. Over-expression of ATF3 in the liver improves lipid homeostasis whereas loss of hepatic ATF3 has opposite effects. In this project, we will investigate whether and how hepatic ATF3 regulates the development of NAFLD. We will use both gain- and loss-of-function approaches to complete this project. Completion of the proposed studies may help identify hepatocyte ATF3 as a key regulator of lipid metabolism and the development of NAFLD.