中文摘要
脂肪组织是人体最大的能量贮存中心,心血管疾病、II型糖尿病以及肥胖等重大代谢疾病都与脂肪组织的功能密切相关。转录因子C/EBP家族和核受体PPARγ是控制脂肪细胞分化和成熟的关键因子。我们前期研究证明Ajuba是一个新发现的PPARγ的共激活因子, 能不依赖于配体而招募组蛋白乙酰化酶CBP/p300激活PPARγ的转录活性,在脂肪细胞的分化中发挥重要作用。目前我们发现Ajuba可以与C/EBPα和C/EBPβ发生相互作用,并能激活C/EBP蛋白的转录活性。这些结果提示Ajuba参与脂肪细胞的分化中多步调控机制。因此,本项研究的目标是:1)确定Ajuba是C/EBP蛋白的转录共激活因子;2)明确Ajuba通过激活 C/EBP转录因子家族和PPARγ的转录活性,实现对脂肪细胞分化的多步调节;3)确定Ajuba是生理状态脂肪组织发育和功能实现的重要调节因子。
英文摘要
Adipose tissue is the largest energy storage reservoir and dysregulation of adipogenesis has been closely related with multiple metabolic diseases including diabetes, cardiovascular diseases and obesity. The C/EBP family of transcription factors and PPAR are critical regulators of adipogenesis. Our preliminary data showed that Ajuba functions as an obligate co-activator of PPARγ and is an important modulator for adipocyte differentiation. Most recently, we found that Ajuba also interacts with C/EBPα and β, and enhances their target gene expression. Together, we hypothesize that Ajuba participates in adipogenesis in multiple steps. Thus, the aims of this proposal are: 1) determine Ajuba is an important co-activator of C/EBPs; 2) determine Ajuba regulates adipogenesis via C/EBPs and PPARγ; 3) Determine the role of Ajuba in regulating adipogenesis in primary adipocytes and mice.
