Exercise alters liver mitochondria phospholipidomic profile and mitochondrial activity in non-alcoholic steatohepatitis

Inês O Gonçalves; Elisabete Maciel; Emanuel Passos; Joan R Torrella; David Rizo; Ginés Viscor; Silvia Rocha-Rodrigues; Estela Santos-Alves; Maria R Domingues; Paulo J Oliveira; António Ascensão; José Magalhães

doi:10.1016/j.biocel.2014.07.011

Exercise alters liver mitochondria phospholipidomic profile and mitochondrial activity in non-alcoholic steatohepatitis

Int J Biochem Cell Biol. 2014 Sep:54:163-73. doi: 10.1016/j.biocel.2014.07.011. Epub 2014 Jul 23.

Affiliations

¹ Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. Electronic address: igoncalvs@gmail.com.
² Mass Spectrometry Centre, Chemistry Department, University of Aveiro, Portugal.
³ Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal.
⁴ Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
⁵ Research Center in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
⁶ CNC - Center for Neurosciences and Cell Biology, University of Coimbra, Portugal.

PMID: 25063232
DOI: 10.1016/j.biocel.2014.07.011

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.

Keywords: Fatty acids; Membrane; NAFLD; Phospholipids; Physical activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Fatty Acids / metabolism*
Male
Membrane Lipids / metabolism*
Mitochondria, Liver / metabolism
Mitochondria, Liver / pathology*
Mitochondrial Membranes / metabolism
Mitochondrial Membranes / pathology*
Non-alcoholic Fatty Liver Disease / metabolism
Non-alcoholic Fatty Liver Disease / pathology*
Oxygen Consumption
Phospholipids / metabolism*
Physical Conditioning, Animal / physiology*
Rats
Rats, Sprague-Dawley

Substances

Fatty Acids
Membrane Lipids
Phospholipids