title: Exercise alters liver mitochondria phospholipidomic profile and mitochondrial activity in non-alcoholic steatohepatitis.
abstract: Mitochondrial membrane lipid composition is a critical factor in non-alcoholic steatohepatitis (NASH). Exercise is the most prescribed therapeutic strategy against NASH and a potential modulator of lipid membrane. Thus, we aimed to analyze whether physical exercise exerted preventive (voluntary physical activity - VPA) and therapeutic (endurance training - ET) effect on NASH-induced mitochondrial membrane changes. Sprague-Dawley rats (n=36) were divided into standard-diet sedentary (SS, n=12), standard-diet VPA (SVPA, n=6), high-fat diet sedentary (HS, n=12) and high-fat diet VPA (HVPA, n=6). After 9 weeks of diet-specific feeding, half of SS and HS group were engaged in an ET program for 8 weeks/5 day/week/1h/day (SET, HET). Liver mitochondria were isolated for oxygen consumption and transmembrane-electric potential (ΔΨ) assays. Mitochondrial phospholipid classes and fatty acids were quantified through thin layer chromatography and gas chromatography, respectively, while cardiolipin (CL), phosphatidylcholine (PC) phosphatidylethanolamine (PE) and phosphatidylinositol (PI) molecular profile was determined by electrospray mass spectrometry. In parallel with histological signs of NASH, high-fat diet decreased PI, CL and PC/PE ratio, whereas PE and phosphatidic acid content increased in sedentary animals (HS vs. SS). Moreover, a decrease in linolelaidic, monounsaturated fatty acids content and an increase in saturated fatty acids (SFAS) were observed. Along with phospholipidomic alterations, HS animals showed a decrease in respiratory control ratio (RCR), ΔΨ and FCCP-induced uncoupling respiration (HS vs. SS). Both phospholipidomic (PC/PE, SFAS) and mitochondrial respiratory alterations were counteracted by exercise interventions. Exercise used as preventive (VPA) or therapeutic (ET) strategies preserved liver mitochondrial phospholipidomic profile and maintained mitochondrial function in a model of NASH.
authors: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. Electronic address: igoncalvs@gmail.com.
authors: Inês O
authors: IO
authors: Gonçalves
authors: Mass Spectrometry Centre, Chemistry Department, University of Aveiro, Portugal.
authors: Elisabete
authors: E
authors: Maciel
authors: Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal.
authors: Emanuel
authors: E
authors: Passos
authors: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors: Joan R
authors: JR
authors: Torrella
authors: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors: David
authors: D
authors: Rizo
authors: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors: Ginés
authors: G
authors: Viscor
authors: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors: Silvia
authors: S
authors: Rocha-Rodrigues
authors: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors: Estela
authors: E
authors: Santos-Alves
authors: Mass Spectrometry Centre, Chemistry Department, University of Aveiro, Portugal.
authors: Maria R
authors: MR
authors: Domingues
authors: CNC - Center for Neurosciences and Cell Biology, University of Coimbra, Portugal.
authors: Paulo J
authors: PJ
authors: Oliveira
authors: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors: António
authors: A
authors: Ascensão
authors: Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors: José
authors: J
authors: Magalhães
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology*; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000473:pathology*; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology*; D010101:Oxygen Consumption; D010743:Phospholipids / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005227:Fatty Acids; D008563:Membrane Lipids; D010743:Phospholipids
keywords: Fatty acids; Membrane; NAFLD; Phospholipids; Physical activity