The Molecular Basis Of SENP2 In Regulation Of Brown Adipogenesis

Brown adipose tissue is a major thermogenic organ that plays a key role in maintenance of body temperature and whole-body energy homeostasis.Brown adipogenesis requires activation of the transcription factor C/EBPb and recruitment of the zinc finger protein Prdm16,but how brown fat lineage is determined is not completely understood.SUMO-Specific Protease SENP2 has been implicated in the regulation of adipogenesis.Here,we show that SUMO-specific protease 2(SENP2),is essential for determining brown fat lineage development.SENP2-Myf5+ lineage knockout mice show severe defects in embryonic and neonatal brown fat formation.Deficiency of SENP2 affects the proliferation,lineage commitment,and terminal differentiation of brown adipocyte precursors.Expression of negative modulator of brown preadipocyte differentiation,Necdin,increased in BAT of embryonic SENP2myf5 cKO mice,which can be regulated by Zfp423.SENP2 desumoylates Zfp423 and modulates brown adipogenesis.The SUMOylation site of Zfp423 is lysine 1136 and SUMOylation of Zfp423 can increase the gene expression and protein level of Necdin,while SENP2 suppresses Necdin expression and facilitates brown adipogenesis by de-SUMOylation of Zfp423.These observations suggest that SENP2 is a key regulator in the determination of brown fat development.