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Int J Cardiol. 2014 Jun 1;174(1):110-8. doi: 10.1016/j.ijcard.2014.03.176. Epub 2014 Apr 8.

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

Author information

1
Department of Pharmacology and Therapeutic Chemistry, IBUB (Institut de Biomedicina de la Universitat de Barcelona), CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Faculty of Pharmacy, University of Barcelona, Diagonal 643, Barcelona E-08028, Spain.
2
Department of Radiation Oncology, Columbia University, P&S 11-451, 630 West 168th Street, New York, NY 10032, USA.
3
Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Quartier UNIL-Sorge, Bâtiment Génopode, CH-1015 Lausanne, Switzerland.
4
Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Quartier UNIL-Sorge, Bâtiment Génopode, CH-1015 Lausanne, Switzerland; Lee Kong Chian School of Medicine, Nanyang Technological University, School of Nursing Building, SGH, Block C, #01-01, 9 Hospital Drive, Singapore 169612, Singapore.
5
Department of Pharmacology and Therapeutic Chemistry, IBUB (Institut de Biomedicina de la Universitat de Barcelona), CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Faculty of Pharmacy, University of Barcelona, Diagonal 643, Barcelona E-08028, Spain. Electronic address: mvazquezcarrera@ub.edu.

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; PPARβ/δ

PMID:
24767130
DOI:
10.1016/j.ijcard.2014.03.176
[Indexed for MEDLINE]

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