Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress
The metabolic associated fatty liver disease (MAFLD) is a public health challenge, leading to a global increase in chronic liver disease. The respiratory exposure of silica nanoparticles (SiNPs) has revealed to induce hepatotoxicity. However, its role in the pathogenesis and progression of MAFLD was...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323172200341X |
| _version_ | 1797954074080968704 |
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| author | Alimire Abulikemu Xinying Zhao Hailin Xu Yan Li Ru Ma Qing Yao Ji Wang Zhiwei Sun Yanbo Li Caixia Guo |
| author_facet | Alimire Abulikemu Xinying Zhao Hailin Xu Yan Li Ru Ma Qing Yao Ji Wang Zhiwei Sun Yanbo Li Caixia Guo |
| author_sort | Alimire Abulikemu |
| collection | DOAJ |
| description | The metabolic associated fatty liver disease (MAFLD) is a public health challenge, leading to a global increase in chronic liver disease. The respiratory exposure of silica nanoparticles (SiNPs) has revealed to induce hepatotoxicity. However, its role in the pathogenesis and progression of MAFLD was severely under-studied. In this context, the hepatic impacts of SiNPs were investigated in vivo and in vitro through using ApoE−/− mice and free fatty acid (FFA)-treated L02 hepatocytes. Histopathological examinations and biochemical analysis showed SiNPs exposure via intratracheal instillation aggravated hepatic steatosis, lipid vacuolation, inflammatory infiltration and even collagen deposition in ApoE−/− mice, companied with increased hepatic ALT, AST and LDH levels. The enhanced fatty acid synthesis and inhibited fatty acid β-oxidation and lipid efflux may account for the increased hepatic TC/TG by SiNPs. Consistently, SiNPs induced lipid deposition and elevated TC in FFA-treated L02 cells. Further, the activation of hepatic oxidative stress was detected in vivo and in vitro, as evidenced by ROS accumulation, elevated MDA, declined GSH/GSSG and down-regulated Nrf2 signaling. Endoplasmic reticulum (ER) stress was also triggered in response to SiNPs-induced lipid accumulation, as reflecting by the remarkable ER expansion and increased BIP expression. More importantly, an UPLC-MS-based metabolomics analysis revealed that SiNPs disturbed the hepatic metabolic profile in ApoE−/− mice, prominently on amino acids and lipid metabolisms. In particular, the identified differential metabolites were strongly correlated to the activation of oxidative stress and ensuing hepatic TC/TG accumulation and liver injuries, contributing to the progression of liver diseases. Taken together, our study showed SiNPs promoted hepatic steatosis and liver damage, resulting in the aggravation of MAFLD progression. More importantly, the disturbed amino acids and lipid metabolisms-mediated oxidative stress was a key contributor to this phenomenon from a metabolic perspective. |
| first_indexed | 2024-04-10T23:12:56Z |
| format | Article |
| id | doaj.art-07c69a5d2b8b4d51b30a23bee2fc2f99 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-10T23:12:56Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-07c69a5d2b8b4d51b30a23bee2fc2f992023-01-13T04:16:15ZengElsevierRedox Biology2213-23172023-02-0159102569Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stressAlimire Abulikemu0Xinying Zhao1Hailin Xu2Yan Li3Ru Ma4Qing Yao5Ji Wang6Zhiwei Sun7Yanbo Li8Caixia Guo9Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, ChinaBeijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, ChinaBeijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, ChinaDepartment of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, ChinaBeijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, ChinaBeijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, ChinaBeijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, ChinaBeijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Corresponding author. Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China.Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Corresponding author. Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China.The metabolic associated fatty liver disease (MAFLD) is a public health challenge, leading to a global increase in chronic liver disease. The respiratory exposure of silica nanoparticles (SiNPs) has revealed to induce hepatotoxicity. However, its role in the pathogenesis and progression of MAFLD was severely under-studied. In this context, the hepatic impacts of SiNPs were investigated in vivo and in vitro through using ApoE−/− mice and free fatty acid (FFA)-treated L02 hepatocytes. Histopathological examinations and biochemical analysis showed SiNPs exposure via intratracheal instillation aggravated hepatic steatosis, lipid vacuolation, inflammatory infiltration and even collagen deposition in ApoE−/− mice, companied with increased hepatic ALT, AST and LDH levels. The enhanced fatty acid synthesis and inhibited fatty acid β-oxidation and lipid efflux may account for the increased hepatic TC/TG by SiNPs. Consistently, SiNPs induced lipid deposition and elevated TC in FFA-treated L02 cells. Further, the activation of hepatic oxidative stress was detected in vivo and in vitro, as evidenced by ROS accumulation, elevated MDA, declined GSH/GSSG and down-regulated Nrf2 signaling. Endoplasmic reticulum (ER) stress was also triggered in response to SiNPs-induced lipid accumulation, as reflecting by the remarkable ER expansion and increased BIP expression. More importantly, an UPLC-MS-based metabolomics analysis revealed that SiNPs disturbed the hepatic metabolic profile in ApoE−/− mice, prominently on amino acids and lipid metabolisms. In particular, the identified differential metabolites were strongly correlated to the activation of oxidative stress and ensuing hepatic TC/TG accumulation and liver injuries, contributing to the progression of liver diseases. Taken together, our study showed SiNPs promoted hepatic steatosis and liver damage, resulting in the aggravation of MAFLD progression. More importantly, the disturbed amino acids and lipid metabolisms-mediated oxidative stress was a key contributor to this phenomenon from a metabolic perspective.http://www.sciencedirect.com/science/article/pii/S221323172200341XSilica nanoparticleHepatotoxicityMetabolomicsMetabolic associated fatty liver diseaseOxidative stress |
| spellingShingle | Alimire Abulikemu Xinying Zhao Hailin Xu Yan Li Ru Ma Qing Yao Ji Wang Zhiwei Sun Yanbo Li Caixia Guo Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress Redox Biology Silica nanoparticle Hepatotoxicity Metabolomics Metabolic associated fatty liver disease Oxidative stress |
| title | Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress |
| title_full | Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress |
| title_fullStr | Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress |
| title_full_unstemmed | Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress |
| title_short | Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress |
| title_sort | silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms mediated oxidative stress |
| topic | Silica nanoparticle Hepatotoxicity Metabolomics Metabolic associated fatty liver disease Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S221323172200341X |
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