Role of physical exercise on hepatic insulin, glucocorticoid and inflammatory signaling pathways in an animal model of non-alcoholic steatohepatitis

LIFE SCIENCES

卷:123

Article

Passos, E.^1,2,3  Pereira, C. D.^1,2  Goncalves, I. O.³  Rocha-Rodrigues, S.³  Silva, N.^4,5  Guimares, J. T.^1,2,4,5  Neves, D.^6,7  Ascensao, A.³  Magalhaes, J.³  Martins, M. J.^1,2 

[1] Univ Porto, Fac Med, Dept Biochem, P-4200450 Oporto, Portugal

[2] Univ Porto, Inst Invest & Inovacao Saude, P-4200450 Oporto, Portugal

[3] Univ Porto, Fac Sport, Res Ctr Phys Act Hlth & Leisure, P-4200450 Oporto, Portugal

[4] Univ Porto, Dept Clin Pathol, Hosp Sao Joao Ctr EPE, P-4200450 Oporto, Portugal

[5] Univ Porto, EPIUnit, Inst Publ Hlth, P-4200450 Oporto, Portugal

[6] Univ Porto, Dept Expt Biol, Fac Med, Inst Invest & Inovacao Saude, P-4200450 Oporto, Portugal

[7] Univ Porto, Inst Mol & Cell Biol IBMC, P-4200450 Oporto, Portugal

关键词: Voluntary physical activity;    Endurance training;    High-fat diet;    Non-alcoholic steatohepatitis;    Inflammation;    Insulin signaling;    Glucocorticoid signaling;   

DOI  :  10.1016/j.lfs.2014.12.013

来源: Elsevier

【 摘 要 】

Aims: Pro-inflammatory mediators, glucocorticoids and transforming growth factor (TGF)-beta 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. Main 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. Key findings: ET improved ISI in both diet regimens. HFD-feeding increased interleukin-1 beta and induced a similar pattern on interleukin-6 and TGF-beta, which were globally reduced by physical exercise. ET decreased HID 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 Ala, and each separately, decreased with exercise and also for activated AKT in SD. Overall, in both diets, exercise reduced 11 beta-hydroxysteroid dehydrogenase type 1. ET increased glucocorticoid receptor and reduced PTP1B in HID. Significance: Physical exercise mitigates the expression of pro-inflammatory mediators and positively modulates insulin and glucocorticoid signaling in NASH. (C) 2014 Elsevier Inc. All rights reserved.

【 授权许可】

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