白色脂肪细胞褐色化可以用于预防和治疗肥胖及其相关代谢疾病，但是其调控机理还有待研究。我们利用可定量研究褐色化的小鼠模型筛选了一系列的转录因子，发现其中Tbx15表达降低能够抑制褐色化并且其高表达可以促进褐色化。已知Tbx15是肥胖症状的标志基因之一，但是其在肥胖发生中的作用还尚未清楚。此外，我们制备的脂肪组织特异性敲除Tbx15的小鼠更易被高脂饲料诱导发生肥胖，而且其脂肪组织的褐色化相关基因表达显著降低；我们前期研究结果表明Tbx15可能通过直接调控白色脂肪细胞褐色化来参与肥胖的发生。本项目拟进一步采用染色质免疫共沉淀和蛋白免疫共沉淀等技术方法开展研究，寻找TBX15的靶基因和互作因子并探寻其与PRDM16的关系，旨在回答Tbx15如何调控白色脂肪细胞褐色化这一关键科学问题。本项目有望阐明Tbx15调控白色脂肪细胞褐色化的分子机理，为其作为肥胖治疗靶点的可能性提供理论依据。

It has been recently reported that browning of white adipose tissues can prevent and treat obesity and its related metabolic disorders in mammalian animals, but the molecular mechanism on browning of white adipocytes remains largely unknown. By screening series of transcriptional factors in Ucp1-luciferase knock-in mouse model, we found that siRNA knockdown of Tbx15 reduced adipocyte browning and its over-expression promoted browning. Tbx15 has been known as a marker gene in obesity, but its role in obesity is poorly known. Besides, the Tbx15 adipose tissue specific knockout mice got obese more easily than control mice on high fat diets and showed reduced browning related genes’ expressions in adipose tissues. These results suggested that Tbx15 may contribute to obesity by regulating browning. Next, chromatin Immunoprecipitation and co-Immunoprecipitation will be used to search for the target genes regulated by Tbx15, the co-activator partners of Tbx15 and its relation with PRDM16, aiming to elucidate the role of Tbx15 in white adipocyte browning. With the above mentioned approaches, we hope to shed more lights on the molecular mechanism of Tbx15 in browning of white adipocytes and its possibility as a potential target for obesity treatment.