title: Role of physical exercise on hepatic insulin, glucocorticoid and inflammatory signaling pathways in an animal model of non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  Pro-inflammatory mediators, glucocorticoids and transforming growth factor (TGF)-β are implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH)-related insulin resistance. As physical activity is beneficial against NASH, we analyzed the voluntary physical activity (VPA) and endurance training (ET) (preventive and therapeutic strategies) effects on hepatic insulin, pro-inflammatory and glucocorticoid signaling regulators/mediators in high-fat (Lieber-DeCarli) diet (HFD)-induced NASH.
  
  
  METHODS
  Adult male Sprague-Dawley rats were divided in standard diet (SD) or HFD, with sedentary, VPA and ET animals in both diet regimens. Plasma glucose and insulin concentrations were analyzed; plasma insulin sensitivity index (ISI) was calculated. Hepatic insulin, pro-inflammatory and glucocorticoid signaling regulators/mediators were evaluated by Western blot or reverse transcriptase-PCR.
  
  
  RESULTS
  ET improved ISI in both diet regimens. HFD-feeding increased interleukin-1β and induced a similar pattern on interleukin-6 and TGF-β, which were globally reduced by physical exercise. ET decreased HFD leukemia inhibitory factor level, SD+VPA animals presenting higher values than HFD+VPA animals. HFD increased the ratio of IRS-1(Ser307)/total IRS-1, which was completely mitigated by physical exercise. Physical exercise reduced total ERK and JNK (total and activated) expression in HFD. In SD vs. HFD, VPA presented higher activated JNK and ET presented higher total JNK. Generally, in HFD, the ratio (activated/total) of AKT, and each separately, decreased with exercise and also for activated AKT in SD. Overall, in both diets, exercise reduced 11β-hydroxysteroid dehydrogenase type 1. ET increased glucocorticoid receptor and reduced PTP1B in HFD.
  
  
  CONCLUSIONS
  Physical exercise mitigates the expression of pro-inflammatory mediators and positively modulates insulin and glucocorticoid signaling in NASH.
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Porto, Portugal. Electronic address: elpassos@hotmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Passos
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
authors.forename: C D
authors.initials: CD
authors.lastname: Pereira
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: I O
authors.initials: IO
authors.lastname: Gonçalves
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: Rocha-Rodrigues
authors.affiliation: Department of Clinical Pathology, Hospital of São João Centre EPE, and EPIUnit, Institute of Public Health, University of Porto, Porto, Portugal.
authors.forename: N
authors.initials: N
authors.lastname: Silva
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; Department of Clinical Pathology, Hospital of São João Centre EPE, and EPIUnit, Institute of Public Health, University of Porto, Porto, Portugal.
authors.forename: J T
authors.initials: JT
authors.lastname: Guimarães
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, Instituto de Investigação e Inovação em Saúde, and Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Neves
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Ascensão
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Magalhães
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
authors.forename: M J
authors.initials: MJ
authors.lastname: Martins
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D005938:Glucocorticoids / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D017931:DNA Primers; D005938:Glucocorticoids; D018836:Inflammation Mediators; D007328:Insulin; D016212:Transforming Growth Factor beta
keywords: Endurance training; Glucocorticoid signaling; High-fat diet; Inflammation; Insulin signaling; Non-alcoholic steatohepatitis; Voluntary physical activity