Forkhead transcription factor Foxo1 is essential for adipocyte differentiation

We analyzed the physiological role of forkhead box class O 1 (Foxo1) in adipocyte differentiation by suppressing Foxo1 mRNA with siRNA specific for Foxo1. Mouse 3T3-L1 preadipocytes infected with an adenovirus expressing Foxo1-siRNA showed a marked decrease in lipid droplet formation when induced to differentiate into adipocytes. Adipocyte differentiation was most severely inhibited by exposing cells to Foxo1-siRNA before induction of differentiation. The incorporation of fluorescent-labeled glucose and fatty acid was significantly inhibited in cells deficient in Foxo1. RT-PCR revealed that downregulation of Foxo1 decreased the expression of the transcription factors, PPAR-gamma and C/EBP-alpha. By comparison, Foxo1-siRNA did not affect the expression of C/EBP-beta or C/EBP-delta during the early period of adipocyte differentiation. These results indicate that Foxo1 plays an essential role in adipocyte differentiation, especially at the very early stage of terminal adipocyte differentiation.