title: Physical exercise prevents and mitigates non-alcoholic steatohepatitis-induced liver mitochondrial structural and bioenergetics impairments.
abstract: Exercise is considered a non-pharmacological tool against several lifestyle disorders in which mitochondrial dysfunction is involved. The present study aimed to analyze the preventive (voluntary physical activity-VPA) and therapeutic (endurance training-ET) role of exercise against non-alcoholic steatohepatitis (NASH)-induced liver mitochondrial dysfunction. Sixty male Sprague-Dawley rats were divided into standard-diet sedentary (SS, n=20), standard-diet VPA (SVPA, n=10), high-fat diet sedentary (HS, n=20) and high-fat diet VPA (HVPA, n=10). After 9weeks of diet-treatment, half of SS and HS animals were engaged in an ET program (SET and HET) for 8weeks, 5days/week and 60min/day. Liver mitochondrial oxygen consumption and transmembrane-electric potential (ΔΨ) were evaluated in the presence of glutamate-malate (G/M), palmitoyl-malate (P/M) and succinate (S/R). Mitochondrial enzymes activity, lipid and protein oxidation, oxidative phosphorylation (OXPHOS) subunits, cytochrome c, adenine nucleotide translocator (ANT) and uncoupling protein-2 (UCP2) content were assessed. HS groups show the histological features of NASH in parallel with decreased ΔΨ and respiratory control (RCR) and ADP/O ratios (G/M and P/M). A state 3 decrease (G/M and S/R), FCCP-induced uncoupling respiration (S/R) and ANT content were also observed. Both exercise types counteracted oxygen consumption (RCR, ADP/O and FCCP-uncoupling state) impairments and improved ΔΨ (lag-phase). In conclusion, exercise prevented or reverted (VPA and ET, respectively) the bioenergetic impairment induced by NASH, but only ET positively remodeled NASH-induced liver structural damage and abnormal mitochondria. It is possible that alterations in inner membrane integrity and fatty acid oxidation may be related to the observed phenotypes induced by exercise.
authors.affiliation: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. Electronic address: igoncalvs@gmail.com.
authors.forename: Inês O
authors.initials: IO
authors.lastname: Gonçalves
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Passos
authors.affiliation: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rocha-Rodrigues
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
authors.forename: Cátia V
authors.initials: CV
authors.lastname: Diogo
authors.affiliation: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors.forename: Joan R
authors.initials: JR
authors.lastname: Torrella
authors.affiliation: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rizo
authors.affiliation: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors.forename: Ginés
authors.initials: G
authors.lastname: Viscor
authors.affiliation: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: Estela
authors.initials: E
authors.lastname: Santos-Alves
authors.affiliation: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Marques-Aleixo
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
authors.affiliation: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Ascensão
authors.affiliation: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Magalhães
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005235:Fatty Liver, Alcoholic / Q000503:physiopathology* / Q000628:therapy; D008099:Liver / Q000473:pathology* / Q000503:physiopathology*; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology* / Q000648:ultrastructure; D010805:Physical Conditioning, Animal; D017207:Rats, Sprague-Dawley
keywords: Hepatic; Mitochondria; NAFLD; Physical activity; Training