EXERCISE AND STATINS. INVESTIGATING THE ROLE OF DAILY PHYSICAL ACTIVITY AND AEROBIC FITNESS ON STATINS TREATMENT-INDUCED MUSCLE DYSFUNCTION

Funder

Organizational Unit

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

Differential Modulation of Cancellous and Cortical Distal Femur by Fructose and Natural Mineral-Rich Water Consumption in Ovariectomized Female Sprague Dawley Rats

Publication . David Guede; Cecília Durães; Inês Brandão; Nuno Silva; Emanuel Passos; Miguel Bernardes; Rosário Monteiro; Maria João Martins; Pereira, Cidália Almeida

Bone mineral density (BMD) and microstructure depend on estrogens and diet. We assessed the impact of natural mineral-rich water ingestion on distal femur of fructose-fed estrogen-deficient female Sprague Dawley rats. Ovariectomized rats drank tap or mineral-rich waters, with or without 10%-fructose, for 10 weeks. A sham-operated group drinking tap water was included (n = 6/group). Cancellous and cortical bone compartments were analyzed by microcomputed tomography. Circulating bone metabolism markers were measured by enzyme immunoassay/enzyme-linked immunosorbent assay or multiplex bead assay. Ovariectomy significantly worsened cancellous but not cortical bone, significantly increased circulating degradation products from C-terminal telopeptides of type I collagen and receptor activator of nuclear factor-kappaB ligand (RANKL), and significantly decreased circulating osteoprotegerin and osteoprotegerin/RANKL ratio. In ovariectomized rats, in cancellous bone, significant water effect was observed for all microstructural properties, except for the degree of anisotropy, and BMD (neither a significant fructose effect nor a significant interaction between water and fructose ingestion effects were observed). In cortical bone, it was observed a significant (a) water effect for medullary volume and cortical endosteal perimeter; (b) fructose effect for cortical thickness, medullary volume, cross-sectional thickness and cortical endosteal and periosteal perimeters; and (c) interaction effect for mean eccentricity. In blood, significant fructose and interaction effects were found for osteoprotegerin (no significant water effect was seen). For the first time in ovariectomized rats, the positive modulation of cortical but not of cancellous bone by fructose ingestion and of both bone locations by natural mineral-rich water ingestion is described

2019-09-30Journal article

Open access