Autor segons l'article: Botteri, Gaia; Salvado, Laia; Guma, Anna; Hamilton, D Lee; Meakin, Paul J; Montagut, Gemma; Ashford, Michael L J; Ceperuelo-Mallafre, Victoria; Fernandez-Veledo, Sonia; Vendrell, Joan; Calderon-Dominguez, Maria; Serra, Dolors; Herrero, Laura; Pizarro, Javier; Barroso, Emma; Palomer, Xavier; Vazquez-Carrera, Manuel
Departament: Bioquímica i Biotecnologia Medicina i Cirurgia Ciències Mèdiques Bàsiques
Autor/s de la URV: Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Vendrell Ortega, Juan José
Paraules clau: Skeletal-muscle Signal transduction Sappβ Sapp? Sapp beta Resistance Pgc-1α Pgc-1? Pgc-1-alpha Pgc-1 alpha Palmitic acid Palmitate Nf-κb Nf-kappa b Nf-?b Muscle, skeletal Muscle fibers, skeletal Mitochondrial-function Mice Male Insulin resistance Insulin Inflammation Humans Hepatic gluconeogenesis Gene-transcription Fatty-acids Endoplasmic-reticulum stress Endoplasmic reticulum stress Creb Cells, cultured Cell line Bace1 protein, mouse Bace1 Aspartic acid endopeptidases Animals Amyloid-beta Amyloid precursor protein secretases Alpha gene pgc-1? palmitate nf-?b insulin resistance creb bace1
Resum: ?-secretase/?-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a key enzyme involved in Alzheimer's disease that has recently been implicated in insulin-independent glucose uptake in myotubes. However, it is presently unknown whether BACE1 and the product of its activity, soluble APP? (sAPP?), contribute to lipid-induced inflammation and insulin resistance in skeletal muscle cells.Studies were conducted in mouse C2C12 myotubes, skeletal muscle from Bace1-/-mice and mice treated with sAPP? and adipose tissue and plasma from obese and type 2 diabetic patients.We show that BACE1 inhibition or knockdown attenuates palmitate-induced endoplasmic reticulum (ER) stress, inflammation, and insulin resistance and prevents the reduction in Peroxisome Proliferator-Activated Receptor ? Co-activator 1? (PGC-1?) and fatty acid oxidation caused by palmitate in myotubes. The effects of palmitate on ER stress, inflammation, insulin resistance, PGC-1? down-regulation, and fatty acid oxidation were mimicked by soluble APP? in vitro. BACE1 expression was increased in subcutaneous adipose tissue of obese and type 2 diabetic patients and this was accompanied by a decrease in PGC-1? mRNA levels and by an increase in sAPP? plasma levels of obese type 2 diabetic patients compared to obese non-diabetic subjects. Acute sAPP? administration to mice reduced PGC-1? levels and increased inflammation in skeletal muscle and decreased insulin sensitivity.Collectively, these findings indicate that the BACE1 product sAPP? is a key determinant in ER stress, inflammation and insulin resistance in skeletal muscle and gluconeogenesis in liver.Copyright © 2018 Elsevier Inc. All rights reserved.
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 0026-0495
Adreça de correu electrònic de l'autor: victoria.ceperuelo@urv.cat sonia.fernandez@urv.cat jvortega@iispv.cat
Identificador de l'autor: 0000-0002-4460-9761 0000-0003-2906-3788 0000-0002-6994-6115
Data d'alta del registre: 2025-02-08
Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
Referència a l'article segons font original: Metabolism Clinical And Experimental. 85 59-75
Referència de l'ítem segons les normes APA: Botteri, Gaia; Salvado, Laia; Guma, Anna; Hamilton, D Lee; Meakin, Paul J; Montagut, Gemma; Ashford, Michael L J; Ceperuelo-Mallafre, Victoria; Fernan (2018). The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling.. Metabolism Clinical And Experimental, 85(), 59-75. DOI: 10.1016/j.metabol.2018.03.005
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2018
Tipus de publicació: Journal Publications
Repositori URV