Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/105878
Title: PPARβ/δ prevents endoplasmic reticulum stress-associated inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism
Authors: Salvadó, Laia
Barroso, Emma
Gómez-Foix, Anna Maria
Palomer, Xavier
Michalik, Liliane
Wahli, Walter
Vázquez-Carrera, Manuel
Keywords: DRNTU::Science::Medicine
Issue Date: 2014
Source: Salvadó, L., Barroso, E., Gómez-Foix, A. M., Palomer, X., Michalik, L., Wahli, W., et al. (2014). PPARβ/δ prevents endoplasmic reticulum stress-associated inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism. Diabetologia, 57(10), 2126-2135.
Series/Report no.: Diabetologia
Abstract: Aim/hypothesis Endoplasmic reticulum (ER) stress, which is involved in the link between inflammation and insulin resistance, contributes to the development of type 2 diabetes mellitus. In this study, we assessed whether peroxisome proliferator-activated receptor (PPAR)β/δ prevented ER stress-associated inflammation and insulin resistance in skeletal muscle cells. Methods Studies were conducted in mouse C2C12 myotubes, in the human myogenic cell line LHCN-M2 and in skeletal muscle from wild-type and PPARβ/δ-deficient mice and mice exposed to a high-fat diet. Results The PPARβ/δ agonist GW501516 prevented lipid-induced ER stress in mouse and human myotubes and in skeletal muscle of mice fed a high-fat diet. PPARβ/δ activation also prevented thapsigargin- and tunicamycin-induced ER stress in human and murine skeletal muscle cells. In agreement with this, PPARβ/δ activation prevented ER stress-associated inflammation and insulin resistance, and glucose-intolerant PPARβ/δ-deficient mice showed increased phosphorylated levels of inositol-requiring 1 transmembrane kinase/endonuclease-1α in skeletal muscle. Our findings demonstrate that PPARβ/δ activation prevents ER stress through the activation of AMP-activated protein kinase (AMPK), and the subsequent inhibition of extracellular-signal-regulated kinase (ERK)1/2 due to the inhibitory crosstalk between AMPK and ERK1/2, since overexpression of a dominant negative AMPK construct (K45R) reversed the effects attained by PPARβ/δ activation. Conclusions/interpretation Overall, these findings indicate that PPARβ/δ prevents ER stress, inflammation and insulin resistance in skeletal muscle cells by activating AMPK.
URI: https://hdl.handle.net/10356/105878
http://hdl.handle.net/10220/20936
DOI: 10.1007/s00125-014-3331-8
Rights: © 2014 Springer-Verlag Berlin Heidelberg. This is the author created version of a work that has been peer reviewed and accepted for publication by Diabetologia, Springer-Verlag Berlin Heidelberg. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1007/s00125-014-3331-8].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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