内脏肥胖是致病根源，糖皮质激素在脂肪重新分布、内脏脂肪蓄积起关键作用，内脏脂肪米色化远低于皮下脂肪与内脏肥胖有关。我们研究已确定GR通过与miR-27b启动子结合调控miR-27b表达抑制脂肪米色化，我们现证实内脏脂肪miR-27b表达高于皮下脂肪，内脏脂肪PDGFRα+祖细胞比例高而皮下脂肪CD137+祖细胞比例高，且GC抑制PDGFRα+祖细胞米色化而对CD137+祖细胞无影响，但miR-27b则能抑制两者米色化，因此我们假设GC差异调控PDGFRα+祖细胞与CD137+祖细胞米色化与GR对miR-27b转录调控的细胞特异性有关，本课题通过基因测序及ATAC-seq motif定位调控位点分析，创新性地从GR与DNA的结合力、与GR结合的GRE位点甲基化及乙酰化以及GR相关转录调控复合体的作用研究GC影响不同脂肪祖细胞的转录差异，明确内脏肥胖根本原因，为治疗内脏肥胖提供新手段。

Visceral obesity is responsible for various diseases. Glucocorticoid plays a key role at fat redistribution and visceral fat accumulation. Visceral obesity is consistent with much lower beiging of visceral fat than that of subcutaneous fat. .We have found that GR inhibits the lipid beiging by regulating miR-27b expression via binding to the miR-27b promoter. Our study confirmed that visceral fat expression of miR-27b higher than subcutaneous fat. While visceral fat contained more PDGFRα+ progenitor cells, subcutaneous fat has a higher proportion of CD137+ progenitor cells. GC inhibited beiging of PDGFRα+ cells but had no effect on CD137+ cells, while miR-27b can suppress the beiging of both. Therefore, we hypothesized that the different effects of GC on the beiging of PDGFRα+ cells and CD137+ cells are related to the cell specificity of GR for miR-27b transcriptional regulation. In this proposal, we intend to work innovatively on the binding of GR to DNA, the methylation and acetylation of GRE binding to GR, and the role of GR-related transcriptional regulation complex through gene sequencing and ATAC-seq motif analysis. Therefore to study the distinct effects of GC among different adipose progenitor cells, defining the underlying mechanism of visceral obesity, and providing new means for the treatment of visceral obesity.