Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected

Autor: Lisbeth H. Olsen, Steen Larsen, Patrick Orlando, Michal Ciborowski, Torben Martinussen, Claus Desler, Tine Lovsø Dohlmann, Trine Pagh Ludvigsen, Lukasz Szczerbinski, Luca Tiano, Liselotte B Christiansen, Adam Kretowski, Ewa Parfieniuk
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Swine
Ubiquinone
Atorvastatin
Mitochondria
Liver
030204 cardiovascular system & hematology
Mitochondrion
Mitochondria
Heart
Protein Carbonylation
chemistry.chemical_compound
0302 clinical medicine
Citrate synthase
Respiratory system
Multidisciplinary
biology
Göttingen minipig
Mitochondria
Experimental models of disease
medicine.anatomical_structure
Metabolome
Swine
Miniature
Medicine
lipids (amino acids
peptides
and proteins)
Oxidation-Reduction
medicine.drug
medicine.medical_specialty
Cell biology
Science
Cell Respiration
Citrate (si)-Synthase
Article
03 medical and health sciences
Internal medicine
Respiration
medicine
Animals
Obesity
Dyslipidaemias
Coenzyme Q10
business.industry
Skeletal muscle
nutritional and metabolic diseases
Energy metabolism
Hydrogen Peroxide
Cardiovascular biology
Mitochondria
Muscle
Oxidative Stress
030104 developmental biology
Endocrinology
chemistry
biology.protein
business
Biomarkers
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
Christiansen, L B, Dohlmann, T L, Ludvigsen, T P, Parfieniuk, E, Ciborowski, M, Szczerbinski, L, Kretowski, A, Desler, C, Tiano, L, Orlando, P, Martinussen, T, Olsen, L H & Larsen, S 2021, ' Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected ', Scientific Reports, vol. 11, 2167 . https://doi.org/10.1038/s41598-021-81846-9
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-021-81846-9
Popis: 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.
Databáze: OpenAIRE
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