Role of ATG14 in the regulation of hepatic function

ATG14在肝功能调节中的作用

• 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
• 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

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 非酒精性脂肪肝（NAFLD）影响美国超过30%的成年人。NAFLD最初表现为 如肝脂肪变性并进展为非酒精性脂肪性肝炎（NASH）、纤维化甚至肝硬化， 肝细胞癌由于疾病的进行性，了解早期 NAFLD发展的致病事件。在这些早期事件中，脂质代谢异常主要是 导致肝脏脂肪变性，表现为肝脏中额外的甘油三酯积累， of lipid脂drops滴.甘油三酯稳态是一个非常动态的过程，因为它涉及生物合成和代谢。 崩溃脂滴动员仍然知之甚少。在这项应用中，研究小组将 研究细胞和动物模型中脂滴分解的调节机制，重点是 一个关键的自噬调节因子-自噬相关14.预计这项研究将提供关键的 对NAFLD治疗性干预和治疗策略的机械见解。