Mediator MED23 links Insulin Signaling to the Adipogenesis Transcription Cascade

Research team led by Dr. Gang Wang at SIBCB recently discovered that the Mediator MED23 links insulin signaling to the adipogenesis transcription cascade. This work was published on Developmental Cell on May 19.

 

Understanding the molecular basis underlying adipocyte differentiation is crucial for better management of obesity and its associated diseases, the prevalence of which has escalated worldwide in recent years. Adipocyte differentiation is orchestrated by multiple signaling pathways and a temporally regulated transcriptional cascade. In this study, Dr. Wang and his colleagues found that the Med23 subunit of the Mediator Complex and its interacting transcription factor Elk1 are critical regulators of adipogenesis. Med23^-/- embryonic fibroblast cells were refractory to hormone-induced adipogenesis. Knockdown of either Med23 or Elk1, or overexpression of dominant-negative Elk1, inhibited adipogenesis. In the absence of either Elk1 or Med23, Krox20, an immediate early gene stimulated by insulin during adipogenesis, was uninducible. Moreover, the adipogenic defect in Med23-deficient cells was rescued by ectopic expression of Krox20 or one of its downstream factors, C/EBPβ or PPARγ. Mechanistically, the insulin-stimulated, Med23-deficient preinitiation complex failed to initiate robust transcription of Krox20.

 

Their results suggest that Med23 serves as a critical link transducing insulin signaling to the transcriptional cascade during adipocyte differentiation; and modulation of the interaction between ELK1 and MED23 may provide the novel strategy to intervene obesity and related diseases.