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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/464bb8e1326e4d41b93a471fef364086
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spelling	oai:doaj.org-article:464bb8e1326e4d41b93a471fef3640862021-12-02T13:57:58ZAtorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected10.1038/s41598-021-81846-92045-2322https://doaj.org/article/464bb8e1326e4d41b93a471fef3640862021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81846-9https://doaj.org/toc/2045-2322Abstract 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.Liselotte Bruun ChristiansenTine Lovsø DohlmannTrine Pagh LudvigsenEwa ParfieniukMichal CiborowskiLukasz SzczerbinskiAdam KretowskiClaus DeslerLuca TianoPatrick OrlandoTorben MartinussenLisbeth Høier OlsenSteen LarsenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	atorvastatin impairs liver mitochondrial function in obese göttingen minipigs but heart and skeletal muscle are not affected
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/464bb8e1326e4d41b93a471fef364086
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Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected

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