Senp2 regulates adipose lipid storage by de-SUMOylation of Setdb1

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2018,（3）
• 页码范围: 258-266
• 页数: 9页
• 语种: 英文
• DOI: 10.1093/jmcb/mjx055

摘要

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 H3Kgme3.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 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 Setdb1 axis in controlling adipose lipid storage.