Conversion of mesenchymal stem cells into terminally differentiated adipocytes progresses sequentially through regulated transcriptional steps. While it is clear that the late phases of adipocyte maturation are governed by the nuclear receptor PPAR?, less is known about the transcriptional control of the initial stages of differentiation. To identify early regulators, we performed a siRNA screen of Forkhead-box genes in adipocytes and show here for the first time that the winged helix factor Foxa3 promotes adipocyte differentiation by cooperating with C/EBPß and d to transcriptionally induce PPAR? expression. Furthermore we demonstrate that mice with genetic ablation of Foxa3 have a selective decrease in epididymal fat depot and a cell-autonomous defect to induce PPAR? specifically in their visceral adipocytes. In obese subjects, FOXA3 is differentially expressed in visceral and subcutaneous adipose depots. Overall our study implicates Foxa3 in the regulation of adipocyte differentiation and depot-selective adipose tissue expansion.
View details for DOI 10.1128/MCB.00244-13
View details for Web of Science ID 000322817600001
View details for PubMedID 23798556