Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected
Abstract Statins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Gö...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-81846-9 |
| _version_ | 1818749715025494016 |
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| author | Liselotte Bruun Christiansen Tine Lovsø Dohlmann Trine Pagh Ludvigsen Ewa Parfieniuk Michal Ciborowski Lukasz Szczerbinski Adam Kretowski Claus Desler Luca Tiano Patrick Orlando Torben Martinussen Lisbeth Høier Olsen Steen Larsen |
| author_facet | Liselotte Bruun Christiansen Tine Lovsø Dohlmann Trine Pagh Ludvigsen Ewa Parfieniuk Michal Ciborowski Lukasz Szczerbinski Adam Kretowski Claus Desler Luca Tiano Patrick Orlando Torben Martinussen Lisbeth Høier Olsen Steen Larsen |
| author_sort | Liselotte Bruun Christiansen |
| collection | DOAJ |
| description | Abstract Statins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs: a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ. |
| first_indexed | 2024-12-18T04:08:11Z |
| format | Article |
| id | doaj.art-464bb8e1326e4d41b93a471fef364086 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:08:11Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-464bb8e1326e4d41b93a471fef3640862022-12-21T21:21:33ZengNature PortfolioScientific Reports2045-23222021-01-0111111510.1038/s41598-021-81846-9Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affectedLiselotte Bruun Christiansen0Tine Lovsø Dohlmann1Trine Pagh Ludvigsen2Ewa Parfieniuk3Michal Ciborowski4Lukasz Szczerbinski5Adam Kretowski6Claus Desler7Luca Tiano8Patrick Orlando9Torben Martinussen10Lisbeth Høier Olsen11Steen Larsen12The LIFEPHARM Centre, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of CopenhagenXlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of CopenhagenGlobal Drug Development, Novo Nordisk A/SClinical Research Centre, Medical University of BialystokClinical Research Centre, Medical University of BialystokClinical Research Centre, Medical University of BialystokClinical Research Centre, Medical University of BialystokCenter for Healthy Aging, Department of Cellular and Molecular Medicine, University of CopenhagenDepartment of Life and Environmental Sciences (DISVA), Polytechnic University of MarcheDepartment of Life and Environmental Sciences (DISVA), Polytechnic University of MarcheDepartment of Public Health, Faculty of Health and Medical Sciences, University of CopenhagenThe LIFEPHARM Centre, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of CopenhagenXlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of CopenhagenAbstract Statins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs: a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ.https://doi.org/10.1038/s41598-021-81846-9 |
| spellingShingle | Liselotte Bruun Christiansen Tine Lovsø Dohlmann Trine Pagh Ludvigsen Ewa Parfieniuk Michal Ciborowski Lukasz Szczerbinski Adam Kretowski Claus Desler Luca Tiano Patrick Orlando Torben Martinussen Lisbeth Høier Olsen Steen Larsen Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected Scientific Reports |
| title | Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected |
| title_full | Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected |
| title_fullStr | Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected |
| title_full_unstemmed | Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected |
| title_short | Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected |
| title_sort | atorvastatin impairs liver mitochondrial function in obese gottingen minipigs but heart and skeletal muscle are not affected |
| url | https://doi.org/10.1038/s41598-021-81846-9 |
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