超氧化物歧化酶3对肥胖症的干预作用及其机制研究

项目名称： 超氧化物歧化酶3对肥胖症的干预作用及其机制研究

项目编号： No.81500650

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 崔冉

作者单位： 同济大学

项目金额： 18万元

中文摘要： 肥胖症发病率高且危害严重，到目前为止还没有特效药物。最新研究发现，超氧化物歧化酶3（SOD3）对肥胖症发生发展的重要环节氧化应激和炎症都具有调节功能，提示其可能具有干预肥胖症的作用。在前期动物实验中，我们发现过表达SOD3基因可以抑制高脂饮食诱导的肥胖、脂肪肝和胰岛素抵抗；机制研究发现，SOD3干预组小鼠与对照组比，脂联素水平升高，推测SOD3可能通过影响脂联素及其下游的炎症和代谢相关基因起到预防肥胖的功能，然而具体机制仍不清楚。本项目拟系统研究SOD3对肥胖症的干预作用，评价体内外环境SOD3对脂质沉积的影响，并对其分子机制进行深入探索，重点侧重于SOD3发挥作用是否通过脂联素来实现。本项目的顺利完成，不仅可以明确SOD3对肥胖症的干预作用，为肥胖症的防治提供新的靶点；还可以拓展对SOD3蛋白功能的认识；同时，进一步加深对氧化应激、炎症在肥胖症发病过程中所发挥作用的了解。

中文关键词： 超氧化物歧化酶3；肥胖；脂肪肝；胰岛素抵抗；脂联素

英文摘要： Obesity is a leading preventable cause of death worldwide and there is no truly effective drug available in the clinic for its treatment. Emerging evidence suggests superoxide dismutase 3 (SOD3) is able to alleviate obesity via its anti-oxidation and anti-inflammation function. In our previous study, we found that Sod3 gene transfer blocked high fat diet induced obesity, fatty liver and insulin resistance. Real-time PCR analysis of adipose and liver tissues revealed that overexpression of the Sod3 gene suppressed expression of pro-inflammatory genes in adipose tissue and enhanced expression of the genes responsible for lipolysis and energy expenditure. And the main possible mechanism is that Sod3 could maintain the adiponectin level in the high fat diet state. The objective of the proposed study is to evaluate the effect of SOD3 for treatment of obesity and to investigate its underlying mechanism. An in vitro lipids aggregation cell model will be developed using mouse 3T3-L1 cells, using which the effect of SOD3 in preventing the differentiation of pre-adipocytes will be evaluated. The obesity mouse model will be established using a high fat diet method, and the therapeutic effect of SOD3 will be assessed using histological staining and biochemical lipid determination. The mechanistic study will be performed towards adiponectin, pivotal factors involved in lipid, glucose and energy metabolism and chronic inflammation. Success of this study will not only recognize SOD3 as a leading molecule for obesity treatment, but also elucidate its underlying mechanism at the molecular and cellular level, and moreover may provide valuable information for discovery of role oxidative stress and chronic inflammation playing in the treatment of obesity.

英文关键词： superoxide dismutase 3;obesity;fatty liver;insulin resistance;adiponectin