肥胖严重影响人类健康，其病因复杂，发现新的肥胖基因和通路是了解肥胖的关键。申请人课题组前期研究发现NINJ2转基因小鼠出现严重肥胖表型，基因敲除小鼠则能够抵抗饮食诱导的肥胖，提示其是一个新的肥胖基因，细胞学研究还发现其与炎症反应相关。本课题拟首先通过人群研究，分析NINJ2对肥胖表型的决定性作用。其次通过小鼠模型，研究NINJ2对各种代谢表型的影响，分析其对炎症反应和肥胖相关病理生理过程的作用，探究其调控肥胖的病理生理机制。再次将分析NINJ2对脂肪细胞增殖、分化、成熟与肥大的影响，研究其对脂肪细胞炎症反应的作用，揭示其调控肥胖的细胞学机制。最后将分析NINJ2上下游分子信号通路及互作蛋白，明确其调控肥胖的分子信号通路。通过以上研究，从群体－个体－组织－细胞－分子层面，阐明NINJ2与炎症反应调控肥胖的详细机理及分子机制，为发现新的肥胖防治手段和治疗靶点打下基础。

Obesity is one of the most important health issue, and the pathology of obesity is complex. Identify the novel causal gene and molecular pathway is the key of revealing the mechanism of obesity. In previous study, the team of the applicant studied the function of NINJ2 gene，and found that it related with inflammation. What is more, the NINJ2 transgenic mice showed serious phenotype of obesity, and NINJ2 KO mice can antagonize the diet induced obesity. These results showed that NINJ2 is a novel susceptibility gene of obesity. The purpose of this project is to reveal the mechanism of NINJ2 caused obesity. For this purpose, first we will perform genetic study in human population, and analyze the relationship between the expression and the variant of NINJ2 with obesity in human. Second, we will analyze the phenotype of NINJ2 TG mice and KO mice, and study the effect of NINJ2 to metabolic traits and the mature, distribution and function of adipose tissue. Third, we will study the effect of NINJ2 to the proliferation,differentiation,mature and hypertrophy of adipocytes. Finally, we will study the pathway and interacted protein of NINJ2. The results of this projects will help us to understand the relationship and the details among NINJ2, inflammation and obesity. This project will also facilitate to identify novel methods and targets of treatment and prevention of obesity.