Distinct Roles of Transcription Factors KLF4, Krox20, and Peroxisome Proliferator-Activated Receptor γ in Adipogenesis

Much of our knowledge on adipogenesis comes from cell culture models of preadipocyte differentiation. Adipogenesis is induced by treating confluent preadipocytes with the adipogenic cocktail, which activates transcription factors (TFs) glucocorticoid receptor (GR) and CREB within minutes and increases expression of TFs C/EBPβ, C/EBPδ, KLF4, and Krox20 within hours. All of these TFs have been shown to be capable of promoting adipogenesis in culture when they are overexpressed. However, it has remained unclear whether endogenous KLF4 and Krox20 are required for adipogenesis in culture and in vivo Using conditional knockout mice and derived white and brown preadipocytes, we show that endogenous KLF4 and Krox20 are dispensable for adipogenesis in culture and for brown adipose tissue development in mice. In contrast, the master adipogenic TF peroxisome proliferator-activated receptor γ (PPARγ) is essential. These results challenge the existing model on transcriptional regulation in the early phase of adipogenesis and highlight the need of studying adipogenesis in vivo.