项目名称: 鞘磷脂合酶2在非酒精性脂肪肝中的作用及机制研究
项目编号: No.31300972
项目类型: 青年科学基金项目
立项/批准年度: 2014
项目学科: 生物科学
项目作者: 李悦
作者单位: 复旦大学
项目金额: 21万元
中文摘要: 本课题以肝脏鞘磷脂合酶2(SMS2)为研究对象,重点考察SMS2活性改变对非酒精性脂肪肝发病过程中的影响,以及从分子水平进行作用机理的探讨。实验利用SMS2基因敲除小鼠和SMS2肝脏转基因小鼠作为SMS2活性缺失和过表达的模型,重点考察肝脏脂质代谢、胰岛素抵抗以及对NAFLD发病状况的影响。力图找出SMS2调控的肝脏靶点基因,以期初步阐明SMS2在NAFLD发生中的作用机制,为更深层探讨NAFLD发病机理并确立SMS作为NAFLD治疗的全新靶点,完善并提供全面的理论依据和实验基础,为筛选NAFLD治疗药物开拓新思路。
中文关键词: 鞘磷脂合酶2;非酒精性脂肪肝;脂质代谢;胰岛素抵抗;
英文摘要: Sphingomyelin sphingolipid de novo biosynthesis is related with nonalcoholic fatty liver disease (NAFLD). However, the mechanism is still unclear. Sphingomyelin synthase (SMS), utilizing ceramide as one of the substrates to produce sphingomyelin, sits at the crossroads of sphingolipid biosynthesis. SMS has two isoforms: SMS1 and SMS2. SMS2 is the major isoform in the liver.To investigate the relationship between liver SMS2 activity-mediated sphingolipid changes and NAFLD, we will utilize two mouse models, SMS2 knockout (KO) mice and SMS2 liver-specific transgenic (LTg) mice.We want to find the effect of liver SMS2 activiy on liver lipid metabolism, insulin resistance(IR) and the development of NAFLD. Above all we will explore the potential mechnisms linking between SMS2 activity and NAFLD.
英文关键词: Sphingomyelin Synthase 2;NAFLD;Lipid Metabolism;Insulin Resistance;