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Role of ATG14 in the regulation of hepatic function

ATG14在肝功能调节中的作用

基本信息

批准号：
10371047
负责人：
X Charlie Dong
金额：
$ 44.13万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10371047
关键词：
Address Adipose tissue Adult Affect Anabolism Animal Model Autophagocytosis Autophagosome Binding Biogenesis Biological Process Cell model Cirrhosis Data Development Diet Disease Event Fatty Liver Fibrosis Functional disorder Genes Genetic Goals Health Hepatic Hepatomegaly Homeostasis Inflammation Investigation Knockout Mice Knowledge Life Light Lipase Lipids Literature Liver Mammals Metabolism Mission Molecular Mus Nature Nutrient Organelles PF4 Gene Pathogenesis Pathogenicity Pathologic Pathway interactions Phospholipids Physiological Physiology Play Prevention Primary carcinoma of the liver cells Process Proteins Public Health Regulation Reporting Research Role Testing Therapeutic Intervention Time Triglycerides United States National Institutes of Health Yeasts base burden of illness chronic liver disease comparative conditional knockout effective therapy fatty liver disease gain of function improved insight knock-down lipid metabolism loss of function monolayer mouse model new therapeutic target non-alcoholic fatty liver disease nonalcoholic steatohepatitis novel overexpression perilipin therapeutic development

项目摘要

Project Summary Nonalcoholic fatty liver disease (NAFLD) affects over 30% adults in the US. The NAFLD initially manifests as hepatic steatosis and progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and even cirrhosis or hepatocellular carcinoma. Due to the progressive nature of the disease, it is crucial to understand the early pathogenic events of the NAFLD development. Among those early events, abnormal lipid metabolism is largely responsible for the hepatic steatosis that is manifested as extra triglyceride accumulation in the liver in the form of lipid droplets. Triglyceride homeostasis is a very dynamic process as it involves both biosynthesis and breakdown. The lipid droplet mobilization remains poorly understood. In this application, the research team will investigate the regulatory mechanisms of lipid droplet breakdown in cellular and animal models with a focus on a key autophagy regulator – autophagy related 14. It is expected that the proposed research will provide key mechanistic insights into the strategy for therapeutic intervention and treatment of NAFLD.

项目摘要在美国，超过30%的成年人患有非酒精性脂肪性肝病(NAFLD)。NAFLD最初表现为随着肝脏脂肪变性并进展为非酒精性脂肪性肝炎(NASH)、纤维化，甚至是肝硬变或肝细胞癌。由于疾病的进行性，了解早期的非酒精性脂肪肝发生的致病事件。在这些早期事件中，脂代谢异常在很大程度上导致肝脏脂肪变性，表现为甘油三酯在肝脏中额外堆积脂滴的数量。甘油三酯的动态平衡是一个非常动态的过程，因为它涉及生物合成和崩溃了。脂滴的动员仍然知之甚少。在此应用程序中，研究团队将在细胞和动物模型中研究脂滴破裂的调节机制，重点是一个关键的自噬调节因子--与自噬相关的14.预计拟议的研究将提供关键对NAFLD治疗干预和治疗策略的机械论见解。