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Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets

Authors :
Sazaki, Iku
Sakurai, Toshihiro
Yamahata, Arisa
Mogi, Sumire
Inoue, Nao
Ishida, Koutaro
Kikkai, Ami
Takeshita, Hana
Sakurai, Akiko
Takahashi, Yuji
1000070197622
Chiba, Hitoshi
1000090337030
Hui, Shu-Ping
Sazaki, Iku
Sakurai, Toshihiro
Yamahata, Arisa
Mogi, Sumire
Inoue, Nao
Ishida, Koutaro
Kikkai, Ami
Takeshita, Hana
Sakurai, Akiko
Takahashi, Yuji
1000070197622
Chiba, Hitoshi
1000090337030
Hui, Shu-Ping
Publication Year :
2023

Abstract

Oxidized low-density lipoproteins (oxLDLs) induce oxidative stress in the liver tissue, leading to hepatic steatosis, inflammation, and fibrosis. Precise information on the role of oxLDL in this process is needed to establish strategies for the prevention and management of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Here, we report the effects of native LDL (nLDL) and oxLDL on lipid metabolism, lipid droplet formation, and gene expression in a human liver-derived C3A cell line. The results showed that nLDL induced lipid droplets enriched with cholesteryl ester (CE) and promoted triglyceride hydrolysis and inhibited oxidative degeneration of CE in association with the altered expression of LIPE, FASN, SCD1, ATGL, and CAT genes. In contrast, oxLDL showed a striking increase in lipid droplets enriched with CE hydroperoxides (CE-OOH) in association with the altered expression of SREBP1, FASN, and DGAT1. Phosphatidylcholine (PC)-OOH/PC was increased in oxLDL-supplemented cells as compared with other groups, suggesting that oxidative stress increased hepatocellular damage. Thus, intracellular lipid droplets enriched with CE-OOH appear to play a crucial role in NAFLD and NASH, triggered by oxLDL. We propose oxLDL as a novel therapeutic target and candidate biomarker for NAFLD and NASH.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1409771740
Document Type :
Electronic Resource