Distinct roles of transcription factors GR, KLF4, Krox20 and PPARg in adipogenesis

Authors

• YK Park
• L Wang
• A Giampietro
• B Lai
• JE Lee
• K Ge

Abstract

Much of our knowledge on adipogenesis comes from cell culture differentiation models such as the widely used 3T3L1 preadipocytes. Adipogenesis is induced by treating confluent 3T3L1 cells with the adipogenic cocktail, which activates transcription factors (TFs) glucocorticoid receptor (GR) and CREB within minutes and increases the expression of TFs C/EBPb/d, KLF4 and Krox20 within hours. This is followed by the induction of two master adipogenic TFs PPARg and C/EBPa. When ectopically expressed in preadipocytes, each of these TFs is capable of promoting adipogenesis in culture. While PPARg and C/EBPa/b/d have been shown to be critical for adipogenesis in mice, it has remained unclear whether endogenous GR, KLF4 and Krox20 are also required for adipogenesis in vivo. Using conditional knockout mice and derived preadipocytes, we demonstrate that endogenous GR is largely dispensable for adipogenesis in culture and brown adipose tissue development in mice. We also show that while endogenous Krox20 and KLF4 are transiently induced in the early phase of adipogenesis in culture, they are dispensable for adipogenesis in vitro and in vivo. These unexpected findings challenge the existing model on transcriptional regulation in the early phase of adipogenesis and highlight the need of studying adipogenesis in vivo.

Scientific Focus Area: Molecular Biology and Biochemistry

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