Mechanisms Underlying the Pathogenesis of Non-alcoholic Fatty Liver Disease

非酒精性脂肪肝发病机制

• 批准号: 10594713
• 负责人: Yanqiao Zhang
• 金额: $ 60.89万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594713
• 关键词: Bile Acid Biosynthesis Pathway; Bile Acids; Binding; Biological Process; C57BL/6 Mouse; Cholestasis; Cholesterol; Cholesterol Homeostasis; Clinical Trials; Complex; Data; Developed Countries; Development; Diet; Endocrine; FDA approved; Fatty acid glycerol esters; Feedback; Fructose; G-Protein-Coupled Receptors; Generations; Genes; Genetic; Goals; Health; Hepatic; Hepatocyte; Homeostasis; Hormones; Human; Hydrogen Peroxide; Inflammation; Integral Membrane Protein; Investigation; Lipolysis; Liver; Liver Cirrhosis; Liver Mitochondria; Malignant neoplasm of liver; Mediating; Metabolic; Mitochondria; Molecular; Mus; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Pharmaceutical Preparations; Play; Primary carcinoma of the liver cells; Production; Protein Family; Proteins; Reactive Oxygen Species; Regulation; Repression; Role; Signal Pathway; Signal Transduction; Steatohepatitis; Superoxides; Synthetic Genes; Triglycerides; absorption; bile acid metabolism; chronic liver disease; db/db mouse; diabetic; fatty acid oxidation; fibrogenesis; hepatocyte nuclear factor; inhibitor; male; new therapeutic target; non-alcoholic fatty liver; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; novel therapeutic intervention; overexpression; prevent; receptor; targeted treatment; uptake; western diet

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.

项目摘要 项目概述：非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病之一 国际吧其致病机制仍不完全清楚。胆汁酸（BA）是内分泌的 对生物过程很重要的激素。BA代谢失调可能导致 BA受体FXR和TGR 5的激活已显示出保护 在小鼠和临床试验中对抗NAFLD。跨膜蛋白141（TMEM 141）属于TMEM蛋白 由大多数功能未知的蛋白质组成的家族。到目前为止，我们还不知道 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。 的NAFLD。我们将研究肝脏TMEM141是否以及如何调节NAFLD的发展， 胆汁酸代谢，以及肝脏TMEM141表达在NAFLD中如何调节。我们将使用一些 转基因小鼠和一种互补的方法来实现我们的目标。