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

Authors :
Iku Sazaki
Toshihiro Sakurai
Arisa Yamahata
Sumire Mogi
Nao Inoue
Koutaro Ishida
Ami Kikkai
Hana Takeshita
Akiko Sakurai
Yuji Takahashi
Hitoshi Chiba
Shu-Ping Hui
Source :
International Journal of Molecular Sciences, Vol 24, Iss 5, p 4281 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 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

Language :
English
ISSN :
14220067 and 16616596
Volume :
24
Issue :
5
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.fe8037afe24047e3846bdc13111554a8
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms24054281