脂肪细胞分化异常是肥胖发生的主要诱因之一。AMPK家族在脂肪代谢中发挥重要作用, 然而AMPKγ2在脂肪细胞分化中的作用尚不清楚。本实验室前期工作发现AMPKγ2的表达随着脂肪细胞的分化显著增加，且敲除AMPKγ2抑制脂肪细胞的分化。核质蛋白分离实验显示AMPKγ2明显定位于成熟脂肪细胞的细胞核内，且诱导α催化亚基的入核。基于这些发现，我们推测AMPKγ2可能是一种新的促进脂肪细胞分化的调控蛋白。本课题拟确定AMPKγ2在体内促进脂肪细胞分化的生理阶段，阐明核定位AMPK为其促进脂肪细胞分化的必要条件，并研究AMPKγ2如何直接与脂肪细胞分化关键转录因子如PPARγ, P300, CEBPα及SREBP-1c等相互结合作用或通过AMPK磷酸化间接影响这些因子的分子机制。本项目的完成将阐明AMPKγ2在脂肪细胞分化中的作用机制，为肥胖及相关疾病的治疗提供新的靶点。

The dysfunction of adipose tissue, especially the abnormal differentiation of adipocytes, is the main cause and underlies pathogenesis for obesity. The role of AMPKγ2 on adipocytes differentiation is still unclear. Previous studies in our laboratory has found that the expression of AMPKγ2 undergone a significant gradual increase during the progression of adipocyte differentiation of adipocytes. Further analysis showed that AMPKγ2 has a positive effect on differentiation of adipocytes, and AMPKγ2 mainly located in the nucleus. Based on these findings, we propose to compare the nuclear localization sequence mutated AMPKγ2 vs. the wild type AMPKγ2 in their ability to rescue adipogenesis in adipose specific AMPK γ2 knockout adipocyte precursor cells, to confirm that the nuclear localization sequence of AMPKγ2 is necessary for AMPK to compartmentalize into the nucleus and promote adipocyte differentiation by phosphorylating key factors such as PPARγ, P300, CEBPα and SREBP-1c etc. This application would, once completed, reveal molecular mechanism of AMPKγ2 in the differentiation of adipocyte, and provide a potentially new target for the treatment of obesity and its related metabolic diseases.