Strategic Project - UI 38 - 2014

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Publications

Physical exercise positively modulates nonalcoholic steatohepatitis‐related hepatic endoplasmic reticulum stress

Publication . Passos, Emanuel; Pereira, Cidália; Gonçalves, Inês O.; Faria, Ana; Ascensão, António; Monteiro, Rosário; Magalhães, José; Martins, Maria J.

Obesity is a predictive factor for the development of nonalcoholic steatohepatitis (NASH). Although some of the mechanisms associated with NASH development are still elusive, its pathogenesis relies on a complex broad spectrum of (interconnected) metabolic-based disorders. We analyzed the effects of voluntary physical activity (VPA) and endurance training (ET), as preventive and therapeutic nonpharmacological strategies, respectively, against hepatic endoplasmic reticulum (ER) stress, ER-related proapoptotic signaling, and oxidative stress in an animal model of high-fat diet (HFD)-induced NASH. Adult male Sprague-Dawley rats were divided into standard control liquid diet (SCLD) or HFD groups, with sedentary, VPA, and ET subgroups in both (sedentary animals with access to SCLD [SS], voluntarily physically active animals with access to SCLD [SV], and endurance-trained animals with access to SCLD [ST] in the former and sedentary animals with access to liquid HFD [HS], voluntarily physically active animals with access to liquid HFD [HV], and endurance-trained animals with access to liquid HFD [HT] in the latter, respectively). Hepatic ER stress and ER-related proapoptotic signaling were evaluated by Western blot and reverse transcriptase-polymerase chain reaction; redox status was evaluated through quantification of lipid peroxidation, protein carbonyls groups, and glutathione levels as well as antioxidant enzymes activity. In SCLD-treated animals, VPA significantly decreased eukaryotic initiation factor-2 alpha (eIF2α). In HFD-treated animals, VPA significantly decreased eIF2α and phospho-inositol requiring enzyme-1 alpha (IRE1α) but ET significantly decreased eIF2α and significantly increased both spliced X-box binding protein 1 (sXBP1) and unspliced X-box binding protein 1; a significant increase of phosphorylated-eIF2α (p-eIF2α) to eIF2α ratio occurred in ET versus VPA. HS compared to SS disclosed a significant increase of total and reduced glutathione, HV compared to SV a significant increase of oxidized glutathione, HT compared to ST a significant increase of p-eIF2α to eIF2α ratio and sXBP1. Physical exercise counteracts NASH-related ER stress and its associated deleterious consequences through a positive and dynamical modulation of the hepatic IRE1α-X-box binding protein 1 pathway.

2022Journal article

Restricted access

Understanding the Metabolic Syndrome Using a Biomedical Chemistry Profile

Publication . Pereira, Cidália; Monteiro, Rosário; Martins, Maria João

2.3.1 Introduction For quite some time, it has been identified that high blood pressure, dyslipidemia [increased triglycerides and reduced high-density lipoprotein (HDL) cholesterol levels], impaired glucose homeostasis and abdominal obesity take place concurrently more than by random, supporting the existence of the metabolic syndrome (MetSyn). Additionally, hyperuricemia, a prothrombotic state, oxidative stress, chronic low grade inflammation, increased levels of apolipoprotein-B and small dense low density lipoprotein (LDL) cholesterol (contributing to atherogenic dyslipidemia), non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis, obstructive sleep apnea and/or polycystic ovarian disease (Fulop, 2006; Alberti, 2009; Roberts, 2009; Ma, 2012; Matsuda, 2013; Mule, 2014; Carson, 2015) are quite often present on the MetSyn, although not yet included in its current/actual definition. Taking this into consideration, it is not surprising that the MetSyn associates with an increased risk of type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (Fulop, 2006; Qiao, 2007; Carson, 2015).

2015Book part

Open access