Sestrin3 in the pathogenesis of alcoholic and non-alcoholic fatty liver disease

Sestrin3 在酒精性和非酒精性脂肪肝发病机制中的作用

• 批准号: 9303199
• 负责人: X Charlie Dong
• 金额: $ 34.91万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303199
• 关键词: 5' -AMP-activated protein kinase; Address; Adult; Alcohol consumption; Alcohols; Animal Model; Autophagocytosis; Autophagosome; Cirrhosis; Complex; Data; Development; Disease; Epidemic; Ethanol; FRAP1 gene; Family member; Fatty Liver; Fibrosis; Functional disorder; Genes; Goals; Health; Hepatic; High Fat Diet; Impairment; Insulin Resistance; Liver; Liver diseases; Mediating; Molecular; Obesity; Oxidoreductase; Pathogenesis; Pathway interactions; Patients; Play; Population; Prevalence; Prevention; Protein Family; Proteins; Public Health; Regulation; Regulatory Pathway; Research; Rodent; Role; Signal Transduction; Steatohepatitis; Testing; Time; Translating; Triglycerides; United States; clinical application; effective therapy; insulin sensitivity; intrahepatic; lipid metabolism; mouse model; non-alcoholic fatty liver; novel; novel therapeutics; overexpression; problem drinker; protein protein interaction; public health relevance; therapeutic development; tissue culture

PROJECT SUMMARY Both alcoholic and non-alcoholic fatty liver diseases (AFLD and NAFLD, respectively) cause serious health problems in the US. AFLD occurs in nearly all excessive alcohol drinkers and NAFLD afflicts approximately one-third of adult population. Worse yet, there is no effective treatment for either AFLD or NAFLD at this time. In this proposed research, we plan to investigate molecular mechanisms of Sestrin3 (Sesn3) in the regulation of hepatic lipid metabolism. There are two specific aims in this project. Aim# 1 is to determine the protective mechanism of Sesn3 against AFLD and NAFLD through the Atg14-regulated autophagy pathway. Aim #2 is to examine the role of Sesn3-mTORC2 pathway in the pathogenesis of AFLD and NAFLD. It is anticipated that the findings from this proposed research should provide valuable information for therapeutic development to treat AFLD and NAFLD.

项目摘要 酒精和非酒精性脂肪肝疾病（分别为AFLD和NAFLD）引起 美国的严重健康问题。 AFLD几乎发生在所有过多的酒精饮用者和NAFLD中 折磨约占成年人口的三分之一。更糟糕的是，这两个都没有有效的治疗方法 此时的AFLD或NAFLD。在这项拟议的研究中，我们计划研究分子机制 Sestrin3（SESN3）的肝脂质代谢调节。这有两个具体的目标 项目。 AIM＃1是通过通过 ATG14调节的自噬途径。 AIM＃2是检查SESN3-MTORC2途径在 AFLD和NAFLD的发病机理。预计这项拟议研究的发现 应提供有价值的信息来治疗AFLD和NAFLD。