Glucocorticoids sensitive progenitor PDGFRa+ cells switching to white adipocytes cause visceral obese via methylation modification of TEAD1 (RNA-seq)
Glucocorticoids have impact on visceral obese which crucial contributor to the burden of obesity complications. Subcutaneous and visceral adipose have the heterogeneity of cellular populations. However, the mechanism of glucocorticoids mediated depot-specific regulation remains unclear. Here, we report PDGFRa+ progenitors, dominated in visceral adipose which can convert to white-typical adipocytes, are glucocorticoid-sensitive progenitors. While CD137+ progenitors, mainly harbored in subcutaneous adipose, which are beige-typical adipocytes, are glucocorticoid-passivated progenitors. Mechanistically, we proved that Glucocorticoids elevate TEAD1, transcriptional coactivator of glucocorticoid receptor, by down-regulating the methylation states in PDGFRa+ progenitors. TEAD1 bonds the accessible binding sites in miR-27b promoter region and transcriptionally increases miR-27b expression which previously proved to be the browning ability inhibitor in human and rodent white adipose. These data provide insight into the mechanism of glucocorticoids mediation of visceral obesity and the pathophysiology of depot-specific variations of high fat diet induced obesity. Overall design: Differentiated CD137+ and PDGFRa+ cells were treated with PBS or Dexamethasone(DEX,1µM). RNA sequencing.