GDF5与PRDM16的交互作用诱导脂肪细胞棕色化的分子机制研究

项目名称： GDF5与PRDM16的交互作用诱导脂肪细胞棕色化的分子机制研究

项目编号： No.81471058

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 罗飞宏

作者单位： 复旦大学

项目金额： 65万元

中文摘要： 肥胖是代谢综合征形成的重要基础。2012年我们首先报道了GDF 5基因与青少年体重相关，后证实GDF 5促进3T3-L1前脂肪细胞有丝分裂期并分化；我们构建了aP2-Gdf5转基因小鼠经PET/CT扫描并结合GDF 5对多能干细胞C3H10T 1/2分化影响的研究，证实GDF 5有诱导脂肪细胞棕色化的作用。我们拟研究GDF 5处理并结合shPRDM16干扰对C3H10T1/2定向分化的影响；以C2C12成肌细胞经梯度GDF 5重组蛋白处理并组合shPRDM16干扰，分析棕色或米色脂肪细胞形成的能力；构建PRDM16基因剔除小鼠，与aP2-Gdf5转基因小鼠杂交获得aP2-Gdf5/Prdm16(-/-)小鼠以进一步了解其脂肪分类和代谢特征并验证二者间的交互作用，较完整揭示GDF 5参与脂肪细胞分化的作用并发现潜在干预靶点。

中文关键词： 肥胖；脂质代谢；脂质生成；生长分化因子5；棕色脂肪

英文摘要： Obesity is the pilot for the formation of the metabolic syndrome. We first reported that the growth differentiation factor 5 (GDF5) gene was associated with the weight of adolescent in 2012, and in the following studies we found that GDF5 proObesity is the pilot for the formation of the metabolic syndrome. We first reported that the growth differentiation factor 5 (GDF5) gene was associated with the weight of adolescent in 2012, and in the following studies we found that GDF5 could promoted 3T3-L1 preadipocytes into mitosis status during its commitment to white adipocytes. We then established aP2-Gdf5 transgenic mice and following PET-CT scan indicated that GDF5 can induce adipocyte cells into brown adipocytes, GDF5 recombinant protein treated pluripotent stem cells C3H10T1/2 showed cytokine marks of brite adipocytes. So, We intend to study the effect of recombinant GDF5 protein combining with shPRDM16 interference on the differentiation procedure of C3H10T1/2 stem cells and its gene expression profile. We also plan to treat C2C12 myoblast with shPRDM16 interference and gradient recombinant GDF5 protein, and then analyze the ability of C2C12 in forming brown or beige adipocytes. Moreover, we will construct PRDM16 knockout mice which will hybridize with the esatablished aP2-GDF5 transgenic mice. After we can obtain aP2-GDF5/PRDM16(-/-) mice, we will further study the animal adipocyte tissue classification and metabolic characteristics, and to verify the interactions between GDF5 and PRDM16. Based on the above experiments, we will be finally able to reveal GDF5 participatory role in adipocyte differentiation and to identify potential targets for intervention.moted 3T3-L1 preadipocytes into mitosis as well as its differentiating into white fat. We then established aP2-GDF5 transgenic mice and sequent PET-CT scan indicated that GDF5 can induce adipocyte cells into brown adipocytes, GDF5 recombinant protein treated pluripotent stem cells C3H10T1/2 showed cytokine marks of brite adipocytes. So, We intend to study the effect of recombinant GDF5 protein combining with shPRDM16 interference on the differentiation procedure of C3H10T1/2 stem cells and its gene expression profile. We also plan to treat C2C12 myoblast with shPRDM16 interference and gradient recombinant GDF5 protein, and then analyze the ability of C2C12 in forming brown or beige adipocytes. Moreover, we will construct PRDM16 knockout mice, hybridizing with constructed aP2-GDF5 transgenic mice, and then we can obtain aP2-GDF5/PRDM16(-/-) mice to further understand their adipocyte tissue classification and metabolic characteristics, and to verify interactions between GDF5 and PRDM16. Based on the above experiments, we will be able to reveal GDF5 participatory role in adipocyte differentiation and to identify potential targets for intervention.

英文关键词： obesity;lipid metabolism;lipogenesis;growth differentiation factor 5;brown fat