Mechanisms Underlying the Pathogenesis of Non-alcoholic Fatty Liver Disease

项目摘要 项目摘要：非酒精性脂肪性肝病是最常见的慢性肝病之一。 全世界。其发病机制尚不完全清楚。胆汁酸(BA)是内分泌的。 对生物过程很重要的激素。BA代谢失调可能会导致 胆汁淤积、肝癌、非酒精性脂肪肝等。BA受体FXR和TGR5的激活已被证明具有保护作用 抗非酒精性脂肪肝的小鼠实验和临床试验。跨膜蛋白141(TMEM141)属于TMEM蛋白 由大部分未知功能的蛋白质组成的家族。到目前为止，人们对这种生物病毒一无所知 TMEM141的功能。在这个项目中，我们计划研究肝脏TMEM141在发病机制中的作用。 非酒精性脂肪肝。我们将研究肝脏TMEM141是否以及如何调节NAFLD和NAFLD的发展 胆汁酸代谢，以及肝脏TMEM141在NAFLD中的表达是如何调节的。我们将使用一些 转基因小鼠和一种实现我们目标的补充方法。

Project Summary Project Summary: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The pathogenic mechanism remains incompletely understood. Bile acids (BAs) are endocrine hormones that are important for the biological processes. Dysregulation of BA metabolism may cause cholestasis, liver cancer, NAFLD, etc. Activation of BA receptors FXR and TGR5 has been shown to protect against NAFLD in mice and clinical trials. Transmembrane protein 141 (TMEM141) belongs to the TMEM protein family that consists of proteins of mostly unknown functions. So far, nothing is known about the biological functions of TMEM141. In this project, we plan to investigate the role of hepatic TMEM141 in the pathogenesis of NAFLD. We will investigate whether and how hepatic TMEM141 regulates the development of NAFLD and bile acid metabolism, and how hepatic TMEM141 expression is regulated in NAFLD. We will use a number of genetically modified mice and a complementary approach to accomplish our goals.