Role of Hepatocyte ATF3 in NAFLD

肝细胞 ATF3 在 NAFLD 中的作用

• 批准号: 10224182
• 负责人: Yanqiao Zhang
• 金额: $ 45.82万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224182
• 关键词: 3' Untranslated Regions; Attenuated; Bile Acids; Binding; Biological Process; Catabolism; Cholesterol; Cholesterol Homeostasis; Cyclic AMP Response Element; Data; Developed Countries; Development; Diabetes Mellitus; Down-Regulation; Family; Fatty Liver; Fibrosis; Gene Expression; Genes; Health; Hepatic; Hepatocyte; High Fat Diet; Homeostasis; Human; Inflammation; Inflammatory Response; Kupffer Cells; Lead; Lipids; Liver; Liver Cirrhosis; Liver diseases; Mediating; Metabolic stress; MicroRNAs; Mus; Obese Mice; Obesity; Pathogenesis; Patients; Pharmacology; Play; Primary carcinoma of the liver cells; Regulation; Repression; Risk Factors; Role; Signal Pathway; Triglyceride Metabolism; Triglycerides; Untranslated RNA; activating transcription factor; activating transcription factor 3; chronic liver disease; diabetic; improved; knock-down; lipid metabolism; liver injury; loss of function; macrophage; member; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; overexpression; prevent; stellate cell; therapeutic target; transcription factor; treatment strategy; western diet

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.

项目摘要 非酒精性脂肪性肝病（NAFLD）是美国最常见的慢性肝病。 在发达国家，其范围从简单的脂肪变性到非酒精性脂肪性肝炎（NASH）。目前为止 NAFLD发展的潜在机制知之甚少。转录激活因子3 （ATF 3）是转录因子的ATF/cAMP反应元件结合（ATF/CREB）家族的成员， 并抑制巨噬细胞中的炎症反应。到目前为止，还没有人知道的作用， 肝脏ATF 3在脂质代谢中的作用。我们的初步研究表明，肝ATF 3表达是 在普通代谢应激下显著降低。肝脏中ATF 3的过度表达可改善血脂 然而，肝脏ATF 3的丧失具有相反的作用。在这个项目中，我们将调查是否和 肝脏ATF 3如何调节NAFLD的发展。我们将同时使用增益函数和损失函数 方法来完成这个项目。完成拟议的研究可能有助于将肝细胞ATF 3鉴定为 脂质代谢和NAFLD发展的关键调节剂。