调节脂肪细胞成脂分化，维持正常的糖脂代谢功能是防治肥胖及相关代谢性疾病的关键。环磷酸腺苷（cAMP）在细胞内由腺苷酸环化酶家族（ADCYs）催化合成，是诱导脂肪细胞分化的必需分子。我们前期研究发现，ADCYs-cAMP信号通路在肥胖小鼠脂肪堆积和胰岛素抵抗方面发挥重要作用；利用siRNA技术下调3T3-L1前体脂肪细胞的ADCY8基因表达，能明显减少成脂分化基因的表达和脂滴形成，但ADCY8在成脂分化过程中的作用及下游分子机制目前国内外均无研究报道。EPAC被认为是cAMP信号下游参与脂肪细胞分化的关键分子，我们利用STRING蛋白相互作用预测网络也发现EPAC与ADCY8存在密切的相互作用。因此，我们拟利用基因干扰和过表达技术，以及ADCY8缺陷小鼠模型，从分子、细胞至动物水平探索ADCY8在脂肪细胞分化及胰岛素信号调控中的作用及分子机制，为防治肥胖相关代谢性疾病提供新的治疗靶点。

Approaches aimed at increasing adipogenesis over adipocyte hypertrophy can now be explored as a strategy to treat obesity and related metabolic diseases. Increase of intracellular cAMP levels is generally considered to be essential for the induction of adipocyte differentiation. In our previous studies, we found that the ADCYs-cAMP signal pathway plays a critical role in fat accumulation and insulin resistance of obese mice. Furthermore, the gene expression of adipogenic and the ability of adipocyte differentiation are decline in ADCY8 gene down-regulated 3T3-L1 preadipocytes. However, the funtion and molecular mechanism of ADCY8 in adipogenesis remains unclear. Previous studies have suggested that activation of EPAC is essential for cAMP-mediated adipocyte differentiation, and the STRING for functional protein association networks predicted that there are intimate interaction between EPAC and ADCY8 protein. So our project is aimed at explored the function and mechanism of ADCY8 in adipocyte differentiation. We will study on the potential molecular pathogenesis of ADCY8 in regulating the adipogenesis and insulin signal by using gene overexpression and RNAi silence methods at molecular, cellular and animal levels. Finally to provide new target in the treatment of obesity and related metabolic diseases.