Triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitis
Objective: Nonalcoholic steatohepatitis is a chronic liver disease caused by the progression of hepatocellular death and inflammation from simple steatosis. However, the pathogenesis of this disease remains unclear. Lipid peroxidation is one of the most critical factors in the development of nonalco...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2024-02-01
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| Series: | Redox Experimental Medicine |
| Subjects: | |
| Online Access: | https://rem.bioscientifica.com/view/journals/rem/2023/1/REM-22-0024.xml |
| _version_ | 1797319306713759744 |
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| author | Kota Saito Yuta Matsuoka Masami Abe Nao Kato Kazushi Morimoto Ken-ichi Yamada |
| author_facet | Kota Saito Yuta Matsuoka Masami Abe Nao Kato Kazushi Morimoto Ken-ichi Yamada |
| author_sort | Kota Saito |
| collection | DOAJ |
| description | Objective: Nonalcoholic steatohepatitis is a chronic liver disease caused by the progression of hepatocellular death and inflammation from simple steatosis. However, the pathogenesis of this disease remains unclear. Lipid peroxidation is one of the most critical factors in the development of nonalcoholic steatohepatitis; however, oxidised lipids – the products of lipid peroxidation – are insufficiently analysed. Here, we comprehensively analysed oxidised lipids in the liver during nonalcoholic steatohepatitis development in a choline-deficient, l-amino acid-defined, high-fat diet-fed mouse model.
Methods: Liver from C57BL/6J mice, fed a standard diet or a choline-defi cient l-amino acid-defined high-fat diet for 1, 3, or 6 weeks, were collected to ev aluate fibrosis, steatosis, inflammation, liver injury, and oxidised lipid production and to observe the suppression of these parameters upon vitamin E administration. In addition, organellar localisation of lipid peroxidation was assessed using fluorescence imaging. Finally, a mitochondria-targeted antioxidant was administered to model mice to investigate the mechanism underlying lipid peroxidation.
Results: We found an accumulation of oxidised triglycerides in the earl y stages of nonalcoholic steatohepatitis. Furthermore, our data indicate that oxidised triglycerides are generated by lipid peroxidation in lipid droplets due to mi tochondria-derived reactive oxygen species.
Conclusion: These results suggest the importance of lipid droplet peroxidation in the progression of nonalcoholic steatohepatitis and may contribute to the development of therapeutic methods for nonalcoholic steatohepatitis in the future.
Significance statement
We demonstrate the specific and early occurrence of lipid peroxidation in nonalcoholic steatohepatitis pathogenesis and propose a previously unknown mechanism of disease progression. |
| first_indexed | 2024-03-08T04:05:00Z |
| format | Article |
| id | doaj.art-ce3134d9d4eb44e6a44a8639ed4effb4 |
| institution | Directory Open Access Journal |
| issn | 2755-158X |
| language | English |
| last_indexed | 2024-03-08T04:05:00Z |
| publishDate | 2024-02-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Redox Experimental Medicine |
| spelling | doaj.art-ce3134d9d4eb44e6a44a8639ed4effb42024-02-09T06:56:20ZengBioscientificaRedox Experimental Medicine2755-158X2024-02-0120231111https://doi.org/10.1530/REM-22-0024Triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitisKota Saito0Yuta Matsuoka1Masami Abe2Nao Kato3Kazushi Morimoto4Ken-ichi Yamada5Department of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, JapanCenter for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, JapanDepartment of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, JapanDepartment of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, JapanDepartment of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, JapanDepartment of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Kyushu University, Maidashi Higashi-ku, Fukuoka, JapanObjective: Nonalcoholic steatohepatitis is a chronic liver disease caused by the progression of hepatocellular death and inflammation from simple steatosis. However, the pathogenesis of this disease remains unclear. Lipid peroxidation is one of the most critical factors in the development of nonalcoholic steatohepatitis; however, oxidised lipids – the products of lipid peroxidation – are insufficiently analysed. Here, we comprehensively analysed oxidised lipids in the liver during nonalcoholic steatohepatitis development in a choline-deficient, l-amino acid-defined, high-fat diet-fed mouse model. Methods: Liver from C57BL/6J mice, fed a standard diet or a choline-defi cient l-amino acid-defined high-fat diet for 1, 3, or 6 weeks, were collected to ev aluate fibrosis, steatosis, inflammation, liver injury, and oxidised lipid production and to observe the suppression of these parameters upon vitamin E administration. In addition, organellar localisation of lipid peroxidation was assessed using fluorescence imaging. Finally, a mitochondria-targeted antioxidant was administered to model mice to investigate the mechanism underlying lipid peroxidation. Results: We found an accumulation of oxidised triglycerides in the earl y stages of nonalcoholic steatohepatitis. Furthermore, our data indicate that oxidised triglycerides are generated by lipid peroxidation in lipid droplets due to mi tochondria-derived reactive oxygen species. Conclusion: These results suggest the importance of lipid droplet peroxidation in the progression of nonalcoholic steatohepatitis and may contribute to the development of therapeutic methods for nonalcoholic steatohepatitis in the future. Significance statement We demonstrate the specific and early occurrence of lipid peroxidation in nonalcoholic steatohepatitis pathogenesis and propose a previously unknown mechanism of disease progression.https://rem.bioscientifica.com/view/journals/rem/2023/1/REM-22-0024.xmlnonalcoholic steatohepatitislipid peroxidationoxidised triglycerides4-hydroxy nonenallipid droplet |
| spellingShingle | Kota Saito Yuta Matsuoka Masami Abe Nao Kato Kazushi Morimoto Ken-ichi Yamada Triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitis Redox Experimental Medicine nonalcoholic steatohepatitis lipid peroxidation oxidised triglycerides 4-hydroxy nonenal lipid droplet |
| title | Triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitis |
| title_full | Triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitis |
| title_fullStr | Triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitis |
| title_full_unstemmed | Triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitis |
| title_short | Triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitis |
| title_sort | triglyceride peroxidation progression in lipid droplets of hepatocytes in nonalcoholic steatohepatitis |
| topic | nonalcoholic steatohepatitis lipid peroxidation oxidised triglycerides 4-hydroxy nonenal lipid droplet |
| url | https://rem.bioscientifica.com/view/journals/rem/2023/1/REM-22-0024.xml |
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