Hepatic FOXA3 Links NAFLD to Atherosclerosis

肝脏 FOXA3 将 NAFLD 与动脉粥样硬化联系起来

• 批准号: 10364733
• 负责人: Yanqiao Zhang
• 金额: $ 51.12万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364733
• 关键词: Ablation; Anti-Inflammatory Agents; Antioxidants; Apolipoprotein A-I; Apolipoprotein E; Arylesterase; Atherosclerosis; Attenuated; Cardiovascular Diseases; Cause of Death; Cessation of life; Cholesterol Homeostasis; Data; Developed Countries; Development; Diabetes Mellitus; Diabetic mouse; Disease; Extrahepatic; Fatty Acids; Genes; HNF4A gene; Health; Hepatic; Hepatocyte; High Density Lipoproteins; High Fat Diet; Human; Incidence; Inflammation; Inflammatory Response; Kupffer Cells; Lead; Link; Lipids; Lipoproteins; Liver; Liver Cirrhosis; Liver Dysfunction; Liver diseases; Low-Density Lipoproteins; Mediating; Metabolic stress; Metabolism; MicroRNAs; Mus; Nuclear Hormone Receptors; Obese Mice; Obesity; Palmitates; Pathogenesis; Patients; Pilot Projects; Plasma; Play; Primary carcinoma of the liver cells; Proteins; Regulation; Repression; Risk Factors; Role; Signal Pathway; Testing; Triglyceride Metabolism; Triglycerides; Very low density lipoprotein; atherogenesis; base; chronic liver disease; db/db mouse; diabetic; improved; insight; knock-down; lipid metabolism; loss of function; member; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; novel therapeutic intervention; overexpression; prevent; reverse cholesterol transport; simple steatosis; stellate cell; transcription factor; transcriptome sequencing; treatment strategy

Project Summary Project Summary: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, which includes simple steatosis (NAFL) and non-alcoholic steatohepatitis (NASH). NAFLD not only causes liver dysfunctions but also induces extra-hepatic complications. Accumulating data indicate that cardiovascular disease (CVD) is the major cause of deaths in NAFLD patients. So far, the mechanism underlying the development of NAFLD is poorly understood. In addition, it is unclear why NAFLD patients have increased incidence of CAD. Forkhead box A3 (FOXA3) is a transcription factor whose function in lipid or lipoprotein metabolism has not been established. Our preliminary studies show that hepatic FOXA3 expression is markedly reduced under common metabolic stress. Using over-expression or knockdown approaches, we show that hepatic FOXA3 regulates hepatic lipid and plasma HDL levels as well as the expression of HDL-associated proteins. These novel data suggest that dysregulation of hepatic FOXA3 may play an important role in the pathogenesis of both NAFLD and CVD. To test this hypothesis, we will use both gain- and loss-of-function approaches. Completion of the proposed studies may uncover a novel role of hepatic FOXA3 in the development of NAFLD and atherosclerosis and may offer novel insights into the mechanism by which NAFLD is a risk factor for CAD.

项目总结