PNPLA7蛋白调控肝脏脂肪代谢和非酒精性脂肪肝病的作用和分子机制

项目名称： PNPLA7蛋白调控肝脏脂肪代谢和非酒精性脂肪肝病的作用和分子机制

项目编号： No.81471079

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李仲

作者单位： 南京医科大学

项目金额： 73万元

中文摘要： 由于机体能量代谢失调导致的代谢综合征极大的危害了人类健康。非酒精性脂肪肝病（NAFLD）是代谢综合征的一个肝脏表现和临床特点。在无过量饮酒史，病毒感染及其他特殊原因时，中性脂肪尤其是甘油三酯在肝脏中堆积是NAFLD的主要特征。NAFLD的发生和肝脏内的很多代谢途径相关，同时又和遗传性的易患病体质和环境因素有关。PNPLA7蛋白是一种未知功能的脂滴蛋白，在肝脏、脂肪组织和肌肉中表达。通过前期研究我们发现在肝脏过表达PNPLA7蛋白可以拮抗高脂饮食导致的肝脏脂肪堆积，显示PNPLA7蛋白在NAFLD的发生以及肝脏脂类新陈代谢调控中发挥着重要作用。我们拟通过使用ob/ob小鼠和建立肝脏PNPLA7转基因小鼠，探讨PNPLA7蛋白在肝脏的生理功能，同时寻找与PNPLA7相互作用蛋白，结合体内外实验确定PNPLA7调控肝脏脂肪代谢 和NAFLD的作用及分子机制，给NAFLD的治疗和预防提供新的靶点。

中文关键词： PNPLA7；非酒精性脂肪肝；胰岛素抵抗；肥胖症；脂质代谢

英文摘要： The metabolic syndrome caused by imbalance of body energy metabolism greatly harm human health. The Non-Alcoholic fatty liver disease （NAFLD） is the liver manifestation and clinical feature of metabolic syndrome. The neutral lipid especially triglyceride accumulated in liver of NAFLD patient in the absence of excessive alcohol consumption, viral infection and other specific reasons. The occurrence of NAFLD associated with not only impaired metabolic process but also genetic predisposition and environmental factor. PNPLA7 is the unknown function lipid droplets associate protein which highly expressed in liver and adipose tissue. The preliminary results of our study show that overexpress PNPLA7 in liver reduces high fat diet induced hepatic lipid accumulation which indicating that PNPLA7 protein plays an important regulatory role in the occurrence of NAFLD and hepatic lipid metabolism . In this project, we will ob/ob mouse and establish PNPLA7 liver specific transgenic mouse as model system to investigate the physiological role of PNPLA7 in regulating hepatic lipid metabolism and find interacting protein of PNPLA7 in liver.We will use biochemstry and molecular biology technique to reveal the physiological function and molecular mechanism of PNPLA7 on hepatic lipid metabolism and NAFLD,thus provide new insight of regulatory network of NAFLD and new target for prevention and treatment of NAFLD and metabolic syndrome.

英文关键词： PNPLA7;NAFLD;Insulin resistance;Obesity;lipid metabolism