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J Mol Cell Biol. 2018 Jun 1;10(3):258-266. doi: 10.1093/jmcb/mjx055.

Senp2 regulates adipose lipid storage by de-SUMOylation of Setdb1.

Zheng Q1,2, Cao Y1,2, Chen Y1,2, Wang J3, Fan Q1,2, Huang X1,2, Wang Y4, Wang T1,2, Wang X1,2, Ma J1,2, Cheng J1,2.

Author information

1
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2
Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
3
Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
4
Cancer Metabolism Laboratory, Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract

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.

PMID:
29272473
DOI:
10.1093/jmcb/mjx055

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