Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model
Mitochondria play an essential role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Previously, we found that succinate-activated respiration was the most affected mitochondrial parameter in mice with mild NAFLD. In this study, we focused on the role of succinate dehydrogenase (SDH)...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| author | Pavla Staňková Otto Kučera Eva Peterová Moustafa Elkalaf David Rychtrmoc Jan Melek Miroslav Podhola Veronika Zubáňová Zuzana Červinková |
| author_facet | Pavla Staňková Otto Kučera Eva Peterová Moustafa Elkalaf David Rychtrmoc Jan Melek Miroslav Podhola Veronika Zubáňová Zuzana Červinková |
| author_sort | Pavla Staňková |
| collection | DOAJ |
| description | Mitochondria play an essential role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Previously, we found that succinate-activated respiration was the most affected mitochondrial parameter in mice with mild NAFLD. In this study, we focused on the role of succinate dehydrogenase (SDH) in NAFLD pathogenesis. To induce the progression of NAFLD to nonalcoholic steatohepatitis (NASH), C57BL/6J mice were fed a Western-style diet (WD) or control diet for 30 weeks. NAFLD severity was evaluated histologically and the expression of selected proteins and genes was assessed. Mitochondrial respiration was measured by high-resolution respirometry. Liver redox status was assessed using glutathione, malondialdehyde, and mitochondrial production of reactive oxygen species (ROS). Metabolomic analysis was performed by GC/MS. WD consumption for 30 weeks led to reduced succinate-activated respiration. We also observed decreased SDH activity, decreased expression of the SDH activator sirtuin 3, decreased gene expression of SDH subunits, and increased levels of hepatic succinate, an important signaling molecule. Succinate receptor 1 (SUCNR1) gene and protein expression were reduced in the livers of WD-fed mice. We did not observe signs of oxidative damage compared to the control group. The changes observed in WD-fed mice appear to be adaptive to prevent mitochondrial respiratory chain overload and massive ROS production. |
| first_indexed | 2024-03-10T10:01:08Z |
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| issn | 1661-6596 1422-0067 |
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| last_indexed | 2024-03-10T10:01:08Z |
| publishDate | 2021-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e990db6079d94ce5b5ee0528f3621b3f2023-11-22T01:57:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213690810.3390/ijms22136908Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD ModelPavla Staňková0Otto Kučera1Eva Peterová2Moustafa Elkalaf3David Rychtrmoc4Jan Melek5Miroslav Podhola6Veronika Zubáňová7Zuzana Červinková8Department of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03 Hradec Králové, Czech RepublicDepartment of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03 Hradec Králové, Czech RepublicDepartment of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03 Hradec Králové, Czech RepublicDepartment of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03 Hradec Králové, Czech RepublicDepartment of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03 Hradec Králové, Czech RepublicDepartment of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03 Hradec Králové, Czech RepublicThe Fingerland Department of Pathology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Czech RepublicDepartment of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03 Hradec Králové, Czech RepublicDepartment of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03 Hradec Králové, Czech RepublicMitochondria play an essential role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Previously, we found that succinate-activated respiration was the most affected mitochondrial parameter in mice with mild NAFLD. In this study, we focused on the role of succinate dehydrogenase (SDH) in NAFLD pathogenesis. To induce the progression of NAFLD to nonalcoholic steatohepatitis (NASH), C57BL/6J mice were fed a Western-style diet (WD) or control diet for 30 weeks. NAFLD severity was evaluated histologically and the expression of selected proteins and genes was assessed. Mitochondrial respiration was measured by high-resolution respirometry. Liver redox status was assessed using glutathione, malondialdehyde, and mitochondrial production of reactive oxygen species (ROS). Metabolomic analysis was performed by GC/MS. WD consumption for 30 weeks led to reduced succinate-activated respiration. We also observed decreased SDH activity, decreased expression of the SDH activator sirtuin 3, decreased gene expression of SDH subunits, and increased levels of hepatic succinate, an important signaling molecule. Succinate receptor 1 (SUCNR1) gene and protein expression were reduced in the livers of WD-fed mice. We did not observe signs of oxidative damage compared to the control group. The changes observed in WD-fed mice appear to be adaptive to prevent mitochondrial respiratory chain overload and massive ROS production.https://www.mdpi.com/1422-0067/22/13/6908nonalcoholic fatty liver diseasemitochondriaoxidative phosphorylationrespirometrysuccinate dehydrogenasesuccinate |
| spellingShingle | Pavla Staňková Otto Kučera Eva Peterová Moustafa Elkalaf David Rychtrmoc Jan Melek Miroslav Podhola Veronika Zubáňová Zuzana Červinková Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model International Journal of Molecular Sciences nonalcoholic fatty liver disease mitochondria oxidative phosphorylation respirometry succinate dehydrogenase succinate |
| title | Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model |
| title_full | Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model |
| title_fullStr | Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model |
| title_full_unstemmed | Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model |
| title_short | Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model |
| title_sort | western diet decreases the liver mitochondrial oxidative flux of succinate insight from a murine nafld model |
| topic | nonalcoholic fatty liver disease mitochondria oxidative phosphorylation respirometry succinate dehydrogenase succinate |
| url | https://www.mdpi.com/1422-0067/22/13/6908 |
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