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Senp2 regulates adipose lipid storage by de-SUMOylation of Setdb1 Free
Quan Zheng 1,2,† , Ying Cao 1,2,† , Yalan Chen 1,2 , Jiqiu Wang 3 , Qiuju Fan 1,2 , Xian Huang 1,2 , Yiping Wang 4 , Tianshi Wang 1,2 , Xiuzhi Wang 1,2 , Jiao Ma 1,2 , and Jinke Cheng 1,2,*
1 Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong
University School of Medicine, Shanghai 200025, China
2 Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025,China
3 Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
4 Cancer Metabolism Laboratory, Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai 200032, China
These authors contributed equally to this work. *Correspondence to:Jinke Cheng, E-mail: jkcheng@shsmu.edu.cn
J Mol Cell Biol, Volume 10, Issue 3, June 2018, Pages 258-266  https://doi.org/10.1093/jmcb/mjx055
Keyword: One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is associated with many pathological conditions including hyperlipidemia, insulin resistance, and type 2 diabetes. In this study, w

One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is associated with many pathological conditions including hyperlipidemia, insulin resistance, and type 2 diabetes. In this study, we observed the overexpression of SUMO-specific protease 2 (Senp2) in adipose tissues during obesity. Adipocyte Senp2 deficiency resulted in less adipose lipid storage accompanied by an ectopic fat accumulation and insulin resistance under high-fat diet feeding. We further found that SET domain bifurcated 1 (Setdb1) was a SUMOylated protein and that SUMOylation promoted Setdb1 occupancy on the promoter locus of Pparg and Cebpa genes to suppress their expressions by H3K9me3. Senp2 could suppress Setdb1 function by de-SUMOylation. In adipocyte Senp2-deficiency mice, accumulation of the SUMOylated Setdb1 suppressed the expression of Pparg and Cebpa genes as well as lipid metabolism-related target genes, which would decrease the ability of lipid storage in adipocytes. These results revealed the crucial role of Senp2–Setdb1 axis in controlling adipose lipid storage.