SENP2 suppresses browning of white adipose tissues by de-conjugating SUMO from C/EBPI3

The adipose tissue is a key site regulating energy metabolism. One of the contributing factors behind this is browning of white adipose tissue (WAT). However, knowledge of the intracellular determinants of the browning process remains incomplete. By generating adipocyte-specific Senp2 knockout (Senp2-aKO) mice, here we show that SENP2 negatively regulates browning by de-conjugating small ubiquitin-like modifiers from C/ EBP beta. Senp2-aKO mice are resistant to diet-induced obesity due to increased energy expenditure and heat production. Senp2 knockout promotes beige adipocyte accumulation in inguinal WAT by upregulation of thermogenic gene expression. In addition, SENP2 knockdown promotes thermogenic adipocyte differentiation of precursor cells isolated from inguinal and epididymal WATs. Mechanistically, sumoylated C/EBP beta, a target of SENP2, suppresses expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBP beta-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT.

Automated summary

The adipose tissue, particularly the browning of white adipose tissue (WAT), plays a crucial role in regulating energy metabolism. This study demonstrates that SENP2 negatively regulates the browning process by de-conjugating small ubiquitin-like modifiers from C/EBP beta. The knockout of Senp2 leads to resistance to diet-induced obesity and the promotion of beige adipocyte accumulation in inguinal WAT. These findings uncover the importance of SENP2 in controlling beige adipogenesis.