Mechanisms Underlying the Pathogenesis of Non-alcoholic Fatty Liver Disease

非酒精性脂肪肝发病机制

基本信息

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
项目类别：
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

项目摘要

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.

项目概要项目概要：非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病之一全世界。其致病机制仍不完全清楚。胆汁酸 (BA) 属于内分泌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、NAFLD 等。BA 受体 FXR 和 TGR5 的激活已被证明可以保护在小鼠中对抗 NAFLD 并进行临床试验。跨膜蛋白141（TMEM141）属于TMEM蛋白由大多数功能未知的蛋白质组成的家族。迄今为止，人们对于生物的生物学特性还一无所知。 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病。我们将研究肝脏 TMEM141 是否以及如何调节 NAFLD 的发展和胆汁酸代谢，以及 NAFLD 中肝脏 TMEM141 表达的调节方式。我们将使用一些转基因小鼠和实现我们目标的补充方法。