| PPARβ/δ activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells. | |
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MedLine Citation:
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PMID: 21070867 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Owing to its high fat content, the classical Western diet has a range of adverse effects on the heart, including enhanced inflammation, hypertrophy, and contractile dysfunction. Proinflammatory factors secreted by cardiac cells, which are under the transcriptional control of nuclear factor-κB (NF-κB), may contribute to heart failure and dilated cardiomyopathy. The underlying mechanisms are complex, since they are linked to systemic metabolic abnormalities and changes in cardiomyocyte phenotype. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate metabolism and are capable of limiting myocardial inflammation and hypertrophy via inhibition of NF-κB. Since PPARβ/δ is the most prevalent PPAR isoform in the heart, we analyzed the effects of the PPARβ/δ agonist GW501516 on inflammatory parameters. A high-fat diet induced the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6, and enhanced the activity of NF-κB in the heart of mice. GW501516 abrogated this enhanced proinflammatory profile. Similar results were obtained when human cardiac AC16 cells exposed to palmitate were coincubated with GW501516. PPARβ/δ activation by GW501516 enhanced the physical interaction between PPARβ/δ and p65, which suggests that this mechanism may also interfere NF-κB transactivation capacity in the heart. GW501516-induced PPARβ/δ activation can attenuate the inflammatory response induced in human cardiac AC16 cells exposed to the saturated fatty acid palmitate and in mice fed a high-fat diet. This is relevant, especially taking into account that PPARβ/δ has been postulated as a potential target in the treatment of obesity and the insulin resistance state. |
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Authors:
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David Alvarez-Guardia; Xavier Palomer; Teresa Coll; Lucía Serrano; Ricardo Rodríguez-Calvo; Mercy M Davidson; Manuel Merlos; Ilhem El Kochairi; Liliane Michalik; Walter Wahli; Manuel Vázquez-Carrera |
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Publication Detail:
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Type: Journal Article Date: 2010-11-09 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1811 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 59-67 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Pharmacology and Therapeutic Chemistry, IBUB (Institut de Biomedicina de la Universitat de Barcelona) and CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)-Instituto de Salud Carlos III, University of Barcelona, Building A, 643 Diagonal, E-08028 Barcelona, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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