Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models
Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, he...
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MDPI AG
2024-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/13/11/1371 |
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| author | Gabriela Svobodová Michaela Šadibolová Eva Velecká Lucia Mráziková Petra Vaculová Petra Matoušková Jaroslav Kuneš Lenka Maletínská Iva Boušová |
| author_facet | Gabriela Svobodová Michaela Šadibolová Eva Velecká Lucia Mráziková Petra Vaculová Petra Matoušková Jaroslav Kuneš Lenka Maletínská Iva Boušová |
| author_sort | Gabriela Svobodová |
| collection | DOAJ |
| description | Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, hepatic metabolic processes, and clearance of therapeutic drugs, respectively. In the MASLD pathogenesis, dysregulated epigenetic mechanisms (e.g., histone modifications, DNA methylation, microRNAs) play a substantial role. In this study, the development of MASLD was investigated in mice fed a high-fat, high-fructose, and high-cholesterol (FFC) diet from 2 months of age, mice treated neonatally with monosodium glutamate (MSG) on a standard diet (STD), and mice treated with MSG on an FFC diet at 7 months of age and compared to control mice (C) on STD. Changes in liver histology, detoxification enzymes, epigenetic regulation, and genes involved in lipid metabolism were characterized and compared. The strong liver steatosis was observed in MSG STD, C FFC, and MSG FFC, with significant fibrosis in the latter one. Moreover, substantial alterations in hepatic lipid metabolism, epigenetic regulatory factors, and expressions and activities of various detoxification enzymes (namely superoxide dismutase, catalase, and carbonyl reductase 1) were observed in MASLD mice compared to control mice. miR-200b-3p, highly significantly upregulated in both FFC groups, could be considered as a potential diagnostic marker of MASLD. The MSG mice fed FFC seem to be a suitable model of MASLD characterized by both liver steatosis and fibrosis and substantial metabolic dysregulation. |
| format | Article |
| id | doaj-art-423a63e8e63d4b019cc0d0d56c0ae851 |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-423a63e8e63d4b019cc0d0d56c0ae8512025-08-20T01:53:52ZengMDPI AGAntioxidants2076-39212024-11-011311137110.3390/antiox13111371Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse ModelsGabriela Svobodová0Michaela Šadibolová1Eva Velecká2Lucia Mráziková3Petra Vaculová4Petra Matoušková5Jaroslav Kuneš6Lenka Maletínská7Iva Boušová8Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 50003 Hradec Králové, Czech RepublicDepartment of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 50003 Hradec Králové, Czech RepublicDepartment of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 50003 Hradec Králové, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16000 Prague, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16000 Prague, Czech RepublicDepartment of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 50003 Hradec Králové, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16000 Prague, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16000 Prague, Czech RepublicDepartment of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 50003 Hradec Králové, Czech RepublicMetabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disorders, is characterized by hepatic lipid accumulation. MASLD causes alterations in the antioxidant defense system, lipid, and drug metabolism, resulting in impaired antioxidant status, hepatic metabolic processes, and clearance of therapeutic drugs, respectively. In the MASLD pathogenesis, dysregulated epigenetic mechanisms (e.g., histone modifications, DNA methylation, microRNAs) play a substantial role. In this study, the development of MASLD was investigated in mice fed a high-fat, high-fructose, and high-cholesterol (FFC) diet from 2 months of age, mice treated neonatally with monosodium glutamate (MSG) on a standard diet (STD), and mice treated with MSG on an FFC diet at 7 months of age and compared to control mice (C) on STD. Changes in liver histology, detoxification enzymes, epigenetic regulation, and genes involved in lipid metabolism were characterized and compared. The strong liver steatosis was observed in MSG STD, C FFC, and MSG FFC, with significant fibrosis in the latter one. Moreover, substantial alterations in hepatic lipid metabolism, epigenetic regulatory factors, and expressions and activities of various detoxification enzymes (namely superoxide dismutase, catalase, and carbonyl reductase 1) were observed in MASLD mice compared to control mice. miR-200b-3p, highly significantly upregulated in both FFC groups, could be considered as a potential diagnostic marker of MASLD. The MSG mice fed FFC seem to be a suitable model of MASLD characterized by both liver steatosis and fibrosis and substantial metabolic dysregulation.https://www.mdpi.com/2076-3921/13/11/1371metabolic dysfunction-associated steatotic liver disease (MASLD)high fat, fructose, and cholesterol (FFC) dietmonosodium glutamate (MSG)detoxification enzymesmiRNAsmice |
| spellingShingle | Gabriela Svobodová Michaela Šadibolová Eva Velecká Lucia Mráziková Petra Vaculová Petra Matoušková Jaroslav Kuneš Lenka Maletínská Iva Boušová Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models Antioxidants metabolic dysfunction-associated steatotic liver disease (MASLD) high fat, fructose, and cholesterol (FFC) diet monosodium glutamate (MSG) detoxification enzymes miRNAs mice |
| title | Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models |
| title_full | Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models |
| title_fullStr | Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models |
| title_full_unstemmed | Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models |
| title_short | Metabolic Dysfunction-Associated Steatotic Liver Disease Is Accompanied by Increased Activities of Superoxide Dismutase, Catalase, and Carbonyl Reductase 1 and Levels of miR-200b-3p in Mouse Models |
| title_sort | metabolic dysfunction associated steatotic liver disease is accompanied by increased activities of superoxide dismutase catalase and carbonyl reductase 1 and levels of mir 200b 3p in mouse models |
| topic | metabolic dysfunction-associated steatotic liver disease (MASLD) high fat, fructose, and cholesterol (FFC) diet monosodium glutamate (MSG) detoxification enzymes miRNAs mice |
| url | https://www.mdpi.com/2076-3921/13/11/1371 |
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