siRNA nanoparticle targeting Usp20 lowers lipid levels and ameliorates metabolic syndrome in mice

Autor: Yi Ding, Qiu-Bing Chen, Hui Xu, Dilare Adi, Yi-Wen Ding, Wen-Jun Luo, Wen-Zhuo Zhu, Jia-Chen Xu, Xiaolu Zhao, Xiong-Jie Shi, Jie Luo, Hao Yin, Xiao-Yi Lu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Lipid Research, Vol 65, Iss 9, Pp 100626- (2024)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1016/j.jlr.2024.100626
Popis: Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr−/− mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.
Databáze: Directory of Open Access Journals