Senp2 regulates adipose lipid storage by de-SUMOylation of Setdbl  

作　　者：Quan Zheng Ying Cao Yalan Chen Jiqiu Wang Qiuju Fan Xian Huang Yiping Wang Tianshi Wang Xiuzhi Wang Jiao Ma Jinke Cheng 

机构地区：[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 liao Tong University School of Medicine, Shanghai 200025 China [3]Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai liao Tong University School of Medicine, Shanghai 200025, China [4]Cancer Metabolism Laboratory, Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai 200032, China

出　　处：《Journal of Molecular Cell Biology》2018年第3期258-266,共9页分子细胞生物学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China （91019021 and 81430069 to J.C.）, the National Basic Research Program of China （973 Program） （2013CB910902 to J.C.）, Shanghai Committee of Science and Technology （15ZR1424500 to T.W. and 15140904300）, Shanghai Municipal Education Commission （ZZjdyx15003 to T.W. and 2017-01-07-00-01-E00050 to J.C.）, and Shanghai Jiao Tong University School of Medicine （14XJ10001 to T.W.）.

摘　　要：One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is asso- ciated 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 5enp2 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 （Setdbl） was a SUMOylated protein and that SUMOylation promoted Setdbl occupancy on the promoter locus of Pparg and Cebpa genes to suppress their expressions by H3Kgme3. Senp2 could suppress Setdbl function by de-SUMOylation. In adipocyte 5enp2-deficiency mice, accumulation of the SUMOylated Setdbl suppressed the expression of Pparg and Cebpo genes as welt as lipid metabolism-related target genes, which would decrease the ability of lipid storage in adipocytes. These results revealed the crucial role of Senp2-Setdbl axis in controlling adipose lipid storage.

关 键 词：lipid storage Senp2 Setdbl H3Kgme3 Pparg and Cebpa 

分 类 号：Q578[生物学—生物化学] TQ658[化学工程—精细化工]