miR-200b/c/429调控棕色脂肪细胞分化的机制研究

Recent studies have demonstrated that there is activated brown adipose tissue (BAT) in human adults. Different with excessive white adipose tissue (WAT) leading to obesity, BAT burn lipids to generate heat and promote energy expenditure. More BAT could prevent obesity and other metabolic disorders. However, the mechanisms which modulate BAT development and differentiation in human adults remain unclear. There is prominent evidence showing that PRDM16 serves as the switch in modulating pluripotent stem cells commitment and differentiation into brow adipocytes. To explore the regulation of PRDM16, we did prediction with bioinformatic tools and found a cluster of microRNAs including miR-200b/c/429, which are highly expressed in WAT but lowly expressed in BAT. These mircoRNAs could target at the 3' untranslated region of PRDM16. In this project, both brown adipocyte differentiation cell model and lentivirous transfection mouse model, which have been well established in our group, will be hired to study the role of miR-200b/c/429 in the regulation of PRDM16 and BAT differentiation. These results could help to clarify the mechanisms of mircoRNA in modulating BAT differentiation and be theoretical basis for new treatment of obesity.

最新的研究发现在成人体内存在有活性的棕色脂肪。与导致肥胖的白色脂肪不同，棕色脂肪能加快脂肪氧化产热，促进机体的能量代谢，体内出现更多的棕色脂肪可以防止肥胖及其相关代谢性疾病的发生。但是目前对于成人体内棕色脂肪细胞分化的调控机制并不明了。研究发现PRDM16在多潜能干细胞定向分化为棕色脂肪还是白色脂肪中起到"调节开关"的重要作用。为了了解对PRDM16的调控机制，我们利用生物信息学技术，发现在白色脂肪高表达而在棕色脂肪低表达的microRNA-200b/c/429能作用于PRDM16的3'端非翻译区。我们计划利用本课题组前期建立的棕色脂肪分化细胞模型及慢病毒转染小鼠模型，研究miR-200b/c/429对棕色脂肪分化和PRDM16的调节作用。研究结果将有助于解释棕色脂肪细胞分化的基因调控机制，为肥胖的防治和新药开发提供理论依据。