Cell Rep. 2022;38(8):110408.
SENP2 suppresses browning of white adipose tissues by de-conjugating SUMO from C/EBPβ.
제1저자 이지선 · 교신저자 정성수, 박경수
소속 (9)
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
- Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Korea.
- Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine, Seoul National University, Seoul, Korea.
- School of Biological Sciences, Seoul National University, Seoul, Korea.
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138667, Singapore; School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine, Seoul National University, Seoul, Korea; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea. Electronic address: suschung@snu.ac.kr.
- Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine, Seoul National University, Seoul, Korea. Electronic address: kspark@snu.ac.kr.
Abstract
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.
Keywords
C/EBPβHOXC10SENP2SUMOadipocytesadipogenesisbrowningobesitythermogenesistranscription
Conflict of interest statement
Declaration of interests The authors declare no competing interest.
그 밖의 정보
- 출판 형태
- Journal Article, Research Support, Non-U.S. Gov't
- 저널
- Cell reports · eISSN 2211-1247
- MeSH
- Adipocytes, Beige* / metabolism · Adipogenesis · Adipose Tissue, Brown / metabolism · Adipose Tissue, White / metabolism · Animals · CCAAT-Enhancer-Binding Protein-beta* / metabolism · Cysteine Endopeptidases* / metabolism · Energy Metabolism / physiology · Mice · Mice, Inbred C57BL · Mice, Knockout · Small Ubiquitin-Related Modifier Proteins* · Thermogenesis / genetics
- Substances
- CCAAT-Enhancer-Binding Protein-beta · Small Ubiquitin-Related Modifier Proteins · Cysteine Endopeptidases · Senp2 protein, mouse