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

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...

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Autores principales: Sazaki, Iku, Sakurai, Toshihiro, Yamahata, Arisa, Mogi, Sumire, Inoue, Nao, Ishida, Koutaro, Kikkai, Ami, Takeshita, Hana, Sakurai, Akiko, Takahashi, Yuji, Chiba, Hitoshi, Hui, Shu-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002183/
https://www.ncbi.nlm.nih.gov/pubmed/36901709
http://dx.doi.org/10.3390/ijms24054281
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author Sazaki, Iku
Sakurai, Toshihiro
Yamahata, Arisa
Mogi, Sumire
Inoue, Nao
Ishida, Koutaro
Kikkai, Ami
Takeshita, Hana
Sakurai, Akiko
Takahashi, Yuji
Chiba, Hitoshi
Hui, Shu-Ping
author_facet Sazaki, Iku
Sakurai, Toshihiro
Yamahata, Arisa
Mogi, Sumire
Inoue, Nao
Ishida, Koutaro
Kikkai, Ami
Takeshita, Hana
Sakurai, Akiko
Takahashi, Yuji
Chiba, Hitoshi
Hui, Shu-Ping
author_sort Sazaki, Iku
collection PubMed
description 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.
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spelling pubmed-100021832023-03-11 Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets Sazaki, Iku Sakurai, Toshihiro Yamahata, Arisa Mogi, Sumire Inoue, Nao Ishida, Koutaro Kikkai, Ami Takeshita, Hana Sakurai, Akiko Takahashi, Yuji Chiba, Hitoshi Hui, Shu-Ping Int J Mol Sci Article 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. MDPI 2023-02-21 /pmc/articles/PMC10002183/ /pubmed/36901709 http://dx.doi.org/10.3390/ijms24054281 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sazaki, Iku
Sakurai, Toshihiro
Yamahata, Arisa
Mogi, Sumire
Inoue, Nao
Ishida, Koutaro
Kikkai, Ami
Takeshita, Hana
Sakurai, Akiko
Takahashi, Yuji
Chiba, Hitoshi
Hui, Shu-Ping
Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets
title Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets
title_full Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets
title_fullStr Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets
title_full_unstemmed Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets
title_short Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets
title_sort oxidized low-density lipoproteins trigger hepatocellular oxidative stress with the formation of cholesteryl ester hydroperoxide-enriched lipid droplets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002183/
https://www.ncbi.nlm.nih.gov/pubmed/36901709
http://dx.doi.org/10.3390/ijms24054281
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