乙酰基转移酶Tip60在高脂饮食调控脂肪代谢中的作用

In our previous study, we have proved that the acetyl transferase Tip60 interacts with USP7 and promote the two rounds of cell cycle in early adipogenesis. Here we propose that Tip60 also has a role in lipid metabolism of mature adipocyte, where it increases basal lipolysis. It is known that PPARγ and Tip60 physically interacts during adipogenesis and we have found that PPARγ is also activating basal lipolysis in mature 3T3-L1 adipocytes. So we hypothesize that Tip60 involved in lipid metabolism through acting as the coactivator of PPARγ. Since we found that knockdown of Tip60 leads to the increase of fat content and lipid droplet size in adipocytes, which is similar to the effect of high fat diet induced obesity in mice. So we will further check the tip60 expression in white adipose tissue of mice with high fat diet to further prove the relavance of Tip60/PPARγ in the molecular mechanism of high fat diet regulation of lipid metabolism. This study would lead to the discovery of a new target for the cure of metabolic diseases like obesity.

之前的研究中，我们发现乙酰基转移酶Tip60在脂肪细胞分化中起到了关键作用，即促进脂肪细胞分化早期的细胞分裂。这里我们提出Tip60除了影响细胞分化还能影响成熟脂肪细胞中的脂肪基础水解，即促进甘油三酯在脂肪细胞中被水解为甘油和游离脂肪酸。而与脂肪代谢功能直接相关的PPARγ同样可以促进脂肪基础水解，而且Tip60和PPARγ同时存在于成熟脂肪细胞的细胞核中，并已知Tip60和PPARγ有互作关系，我们因此推测Tip60是作为PPARγ的coactivator参与脂肪代谢调控。同时因为Tip60 knockdown导致的脂肪含量增高脂滴增大等现象与高脂饮食效果相似。我们将进一步证实高脂饮食与Tip60表达之间的相关性。从而提出Tip60/PPARγ可能与高脂饮食调节脂肪代谢的分子机制相关。因此，对Tip60/PPARγ在脂肪代谢中作用的研究将对开发肥胖症等代谢疾病的新药提供新靶点。