脂肪细胞分化是脂肪组织发育的重要组成部分,与肥胖和肥胖相关疾病密切相关。在这项研究中,我们发现PPARγ的表达,在3T3-L1细胞分化的第5-7天,RUVBL2和脂联素同时明显增加。PPARγ过表达或PPARγ激活剂促进脂联素运输和分泌,并在3T3-L1细胞成脂分化过程中上调RUVBL2表达以及AS160磷酸化。持续的RUVBL2过表达也增强了脂联素的聚合和分泌,相比之下,RUVBL2敲低降低脂联素分泌。Further,PPARγ显著增强RUVBL2启动子活性和转录。RUVBL2启动子对PPARγ结合位点的逐渐缺失和突变表明,位于-804/-781bp的PPARγ结合基序是RUVBL2启动子活性所需的必需成分。染色质免疫沉淀(ChIP)测定确定PPARγ可以直接与RUVBL2启动子DNA相互作用。一起来看,这些数据表明PPARγ促进表达,通过转录激活RUVBL2聚合和分泌脂联素,加速3T3-L1细胞分化。
Adipocyte differentiation is an essential part of adipose tissue development, and is closely related to obesity and obesity-related diseases. In this study, we found that the expression of PPARγ,
RUVBL2 and Adiponectin were concurrently obviously increased in the 5th-7th day of 3T3-L1 cell differentiation. PPARγ overexpression or the PPARγ activator facilitated Adiponectin trafficking and secretion and upregulated RUVBL2 expression as well as AS160 phosphorylation during adipogenic differentiation of 3T3-L1 cells. Consistently
RUVBL2 overexpression also enhanced the polymerization and secretion of Adiponectin, in contrast,
RUVBL2 knockdown reduced Adiponectin secretion. Further, PPARγ significantly enhanced
RUVBL2 promoter activity and transcription. The progressive deletions and mutations of
RUVBL2 promoter for PPARγ binding sites suggested that the PPARγ binding motif situated at -804/-781 bp is an essential component required for RUVBL2 promoter activity. Chromatin immunoprecipitation (ChIP) assays determined that PPARγ can directly interact with the RUVBL2 promoter DNA. Taken together, these data suggest that PPARγ promotes the expression, polymerization and secretion of Adiponectin by activating RUVBL2 transcriptionally, which accelerates 3T3-L1 cell differentiation.