核受体COUP-TFIII促进非酒精性脂肪性肝病发生发展的作用及机制研究

非酒精性脂肪性肝病（NAFLD）与2型糖尿病、肝脏疾病均密切相关。然而其发病机制尚未完全阐明。在前期工作中，我们发现：肥胖小鼠和NAFLD患者肝脏组织中核受体COUP-TFIII的表达显著上调。通过腺相关病毒系统在C57BL/6小鼠肝脏特异性过表达COUP-TFIII基因后，肝脏甘油三酯和游离脂肪酸含量增多，RNA-Sequencing结果表明：负责游离脂肪酸摄取的CD36表达明显上调。因此我们推测核受体COUP-TFTII可能通过诱导CD36的表达促进NAFLD的发生和发展。本项目将在上述研究结果的基础上，进一步探究COUP-TFIII促进NAFLD发生发展的作用及具体机制。本项目的开展不仅为NAFLD病理生理学研究提供新的视角，同时也为将来开展靶向治疗提供了新的科学依据。

Non-alcoholic fatty liver disease is closely related to type 2 diabetes and liver diseases. However, the underlying molecular basis is unclear. We discovered significant up-regulation of COUP-TFIII in livers of obese mice and patients with non-alcoholic fatty liver disease. By using the adeno-associated virus system, we got liver-specific overexpression of COUP-TFIII mice. Contents of free fatty acid and triglyceride in liver-specific overexpression of COUP-TFIII mice were significantly up-regulated. RNA-Sequencing analysis showed CD36 expression associated with free fatty acid uptake was significantly up-regulated as well. Therefore, we speculate COUP-TFIII may promote the onset of non-alcoholic fatty liver disease through up-regulation of CD36. This project will further explore the role of COUP-TFIII in non-alcoholic fatty liver disease. This project will provide novel information on the pathophysiology of non-alcoholic fatty liver disease. Such information may provide a new basis for the targeted therapy of non-alcoholic fatty liver disease in the future.