PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells.

Details

Serval ID
serval:BIB_DD97833B580F
Type
Article: article from journal or magazin.
Collection
Publications
Title
PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells.
Journal
International Journal of Cardiology
Author(s)
Palomer X., Capdevila-Busquets E., Botteri G., Salvadó L., Barroso E., Davidson M.M., Michalik L., Wahli W., Vázquez-Carrera M.
ISSN
1874-1754 (Electronic)
ISSN-L
0167-5273
Publication state
Published
Issued date
2014
Volume
174
Number
1
Pages
110-118
Language
english
Abstract
BACKGROUND: Chronic endoplasmic reticulum (ER) stress contributes to the apoptotic cell death in the myocardium, thereby playing a critical role in the development of cardiomyopathy. ER stress has been reported to be induced after high-fat diet feeding in mice and also after saturated fatty acid treatment in vitro. Therefore, since several studies have shown that peroxisome proliferator-activated receptor (PPAR)β/δ inhibits ER stress, the main goal of this study consisted in investigating whether activation of this nuclear receptor was able to prevent lipid-induced ER stress in cardiac cells.
METHODS AND RESULTS: Wild-type and transgenic mice with reduced PPARβ/δ expression were fed a standard diet or a high-fat diet for two months. For in vitro studies, a cardiomyocyte cell line of human origin, AC16, was treated with palmitate and the PPARβ/δ agonist GW501516. Our results demonstrate that palmitate induced ER stress in AC16 cells, a fact which was prevented after PPARβ/δ activation with GW501516. Interestingly, the effect of GW501516 on ER stress occurred in an AMPK-independent manner. The most striking result of this study is that GW501516 treatment also upregulated the protein levels of beclin 1 and LC3II, two well-known markers of autophagy. In accordance with this, feeding on a high-fat diet or suppression of PPARβ/δ in knockout mice induced ER stress in the heart. Moreover, PPARβ/δ knockout mice also displayed a reduction in autophagic markers.
CONCLUSION: Our data indicate that PPARβ/δ activation might be useful to prevent the harmful effects of ER stress induced by saturated fatty acids in the heart by inducing autophagy.
Keywords
Autophagy, Diabetic cardiomyopathy, Endoplasmic reticulum stress, PPAR beta/delta
Pubmed
Web of science
Create date
26/06/2014 10:08
Last modification date
20/08/2019 17:02
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