Senp7 Deficiency Impairs Lipid Droplets Maturation in White Adipose Tissues via Plin4 DeSUMOylation

Jingwen Pei; Dayuan Zou; Lu Li; Lulu Kang; Minli Sun; Xu Li; Qianyue Chen; Danning Chen; Bin Qu; Xiang Gao; Zhaoyu Lin

doi:10.1016/j.jbc.2024.107319

Senp7 Deficiency Impairs Lipid Droplets Maturation in White Adipose Tissues via Plin4 DeSUMOylation

J Biol Chem. 2024 Apr 25:107319. doi: 10.1016/j.jbc.2024.107319. Online ahead of print.

Authors

Jingwen Pei¹, Dayuan Zou², Lu Li¹, Lulu Kang¹, Minli Sun¹, Xu Li³, Qianyue Chen¹, Danning Chen¹, Bin Qu⁴, Xiang Gao⁵, Zhaoyu Lin⁶

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology, Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National resource center for mutant mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210061, China.
² State Key Laboratory of Pharmaceutical Biotechnology, Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National resource center for mutant mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210061, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui, China.
³ Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
⁴ Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany.
⁵ State Key Laboratory of Pharmaceutical Biotechnology, Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National resource center for mutant mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210061, China. Electronic address: gaoxiang@nju.edu.cn.
⁶ State Key Laboratory of Pharmaceutical Biotechnology, Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National resource center for mutant mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210061, China. Electronic address: linzy@nju.edu.cn.

PMID: 38677512
DOI: 10.1016/j.jbc.2024.107319

Abstract

Lipid metabolism is important for the maintenance of physiological homeostasis. Several members of the SUMO-specific protease (SENP) family have been reported as the regulators of lipid homeostasis. However, the function of Senp7 in lipid metabolism remains unclear. In this study, we generated both conventional and adipocyte-specific Senp7 knockout mice to characterize the role of Senp7 in lipid metabolism homeostasis. Both Senp7-deficient mice displayed reduced white adipose tissue mass and decreased size of adipocytes. By analyzing the lipid droplet morphology, we demonstrated that the lipid droplet size was significantly smaller in Senp7-deficient adipocytes. Mechanistically, Senp7 could deSUMOylate the perilipin family protein Plin4 to promote the lipid droplet localization of Plin4. Our results reveal an important role of Senp7 in the maturation of lipid droplets via Plin4 deSUMOylation.

Keywords: DeSUMOylation; Plin4; Senp7; lipid droplet; lipid storage.