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

Ji Seon Lee, Sehyun Chae, Jinyan Nan, Young Do Koo, Seung-Ah Lee, Young Joo Park, Daehee Hwang, Weiping Han, Dong-Sup Lee, Young-Bum Kim, Sung Soo Chung, Kyong Soo Park

Cell reports 2022 Feb 22

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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/EBPβ. 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/EBPβ, a target of SENP2, suppresses expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBPβ-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Ji Seon Lee, Sehyun Chae, Jinyan Nan, Young Do Koo, Seung-Ah Lee, Young Joo Park, Daehee Hwang, Weiping Han, Dong-Sup Lee, Young-Bum Kim, Sung Soo Chung, Kyong Soo Park. SENP2 suppresses browning of white adipose tissues by de-conjugating SUMO from C/EBPβ. Cell reports. 2022 Feb 22;38(8):110408