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

被引:10
|
作者
Sazaki, Iku [1 ]
Sakurai, Toshihiro [1 ]
Yamahata, Arisa [1 ]
Mogi, Sumire [1 ]
Inoue, Nao [1 ]
Ishida, Koutaro [1 ]
Kikkai, Ami [1 ]
Takeshita, Hana [1 ]
Sakurai, Akiko [1 ]
Takahashi, Yuji [2 ]
Chiba, Hitoshi [3 ]
Hui, Shu-Ping [1 ]
机构
[1] Hokkaido Univ, Fac Hlth Sci, Sapporo 0600812, Japan
[2] Hlth Sci Univ Hokkaido, Sch Med Technol, Sapporo 0028072, Japan
[3] Sapporo Univ Hlth Sci, Dept Nutr, Sapporo 0070894, Japan
基金
日本学术振兴会;
关键词
LDL; non-alcoholic steatohepatitis; non-alcoholic fatty liver disease; liquid chromatography-mass spectrometry; lipidomics; FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; DIET; ACCUMULATION; EXPRESSION; PRODUCTS; LDL;
D O I
10.3390/ijms24054281
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:15
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