MicroRNA-199a调控脂肪细胞分化及在肥胖发生中的作用和机制研究

我国肥胖患者人数近年来迅速增加。肥胖是多种疾病的共同病理基础，包括2型糖尿病、心脑血管疾病、肿瘤等，已严重威胁人类健康。肥胖的发生与脂肪细胞分化密切相关。miR-199a是新近发现的一类小分子RNA家族的成员之一。我们在已经成功构建的miR-199a敲除小鼠模型中，观察到脂肪细胞体积变大，脂滴增多。在预实验中我们发现，参与脂肪分化的关键基因PPARγ2的表达显著升高，提示miR-199a对脂肪分化及肥胖的发生具有重要调控作用。在这些重要发现的基础上，为进一步验证该假设，拟综合运用多种实验技术，如蛋白免疫共沉淀，细胞转染，病毒构建，Luciferase报告基因检测等，在细胞，分子和动物整体水平，深入探讨miR-199a与脂肪含量关系，明确miR-199a与脂肪细胞分化相关关键基因表达的关系及对动物整体功能的影响。通过上述研究，为深入理解脂肪分化障碍相关的肥胖等疾病机制及治疗提供理论依据。

Obesity has become an important public health problem because of its high prevalence worldwide. The number of obese people in China is growing even faster. Obesity is tightly associated with type 2 diabetes, cardiovasculardisease, fatty liver and tumor. The hallmark feature of obesity is the increased adipose tissues. In our previous studies, we observed that miR-199a might play an important role in the adipocyte differentiation. The lipid droplet and adipocyte volume were markedly increased in miR-199a knockout mice, compared with wild-type littermates. In addition, our preliminary data showed that the expression levels of key adipogenic genes were also elevated in knockouts. Based on these findings, we will further focus on :1) the roles and mechanisms of miR-199a in the adipocyte differentiation; 2) the relationship between miR-199a and adipose triglyceride contents. 3) the relationship between miR-199a and obesity. These results will help to identify new regulatory pathways and mechanisms in the adipocyte differentiation, which will be of benefit to seek potential therapeutic targets for obesity and insulin resistance.