| Title: | Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets |
| Authors: | Sazaki, Iku Browse this author |
| Sakurai, Toshihiro Browse this author |
| Yamahata, Arisa Browse this author |
| Mogi, Sumire Browse this author |
| Inoue, Nao Browse this author |
| Ishida, Koutaro Browse this author |
| Kikkai, Ami Browse this author |
| Takeshita, Hana Browse this author |
| Sakurai, Akiko Browse this author |
| Takahashi, Yuji Browse this author |
| Chiba, Hitoshi Browse this author →KAKEN DB |
| Hui, Shu-Ping Browse this author →KAKEN DB |
| Keywords: | LDL |
| non-alcoholic steatohepatitis |
| non-alcoholic fatty liver disease |
| liquid chromatography-mass spectrometry |
| lipidomics |
| Issue Date: | 21-Feb-2023 |
| Publisher: | MDPI |
| Journal Title: | International Journal of Molecular Sciences |
| Volume: | 24 |
| Issue: | 5 |
| Start Page: | 4281 |
| Publisher DOI: | 10.3390/ijms24054281 |
| PMID: | 36901709 |
| 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/89091 |
| Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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