The transient expression of Klf4 and Klf5 during adipogenesis depends on GSK3β activity

Abstract

Adipogenesis is regulated by a complex cascade of transcriptional factors, among them KLF4. This factor was previously shown to be necessary for adipose differentiation. We found that GSK3β activity was required for Klf4 and Klf5 expression during adipogenesis. In addition, retinoic acid inhibited Klf4 and Klf5 expression but not that of Cebpb. Protein synthesis inhibition showed that the transient expression of Klf4, Cebpb and Klf5 during early adipogenesis seemed to require a yet unknown protein for their repression. We also found that Klf4 forced expression in 3T3-F442A cells cultured under non-adipogenic conditions did not induce adipogenesis, nor the expression of Cebpb or Klf5, a Cebpb target gene, showing that KLF4 was not sufficient for adipose differentiation to take place. This would suggest that a more complex combination of molecular pathways not yet understood, is involved during early adipogenesis.

Keywords:

• adipogenesis
• Cebpb
• differentiation
• GSK3
• Klf4
• Klf5
• retinoic acid

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Juan Pedro Arias Luna, Nicolás Villegas Sepúlveda, and Alejandra Aguilar Martinez for their advice. We also thank Raúl Bonilla Moreno and Manuel Flores Cano for their excellent technical assistance; Victor Hugo Rosales from UCF for flow cytometry service, María Guadalupe Aguilar González for sequencing service, Alberto Rodriguez for his technical assistance and the secretarial assistance of Maria Elena Rojano.

Funding

This study was supported by CONACYT scholarship 203665 and grant 104350.