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PPARβ/δ activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2011 Feb; Vol. 1811 (2), pp. 59-67. Date of Electronic Publication: 2010 Nov 09. - Publication Year :
- 2011
-
Abstract
- 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.<br /> (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- AMP-Activated Protein Kinases metabolism
Animals
Cell Line
Cells, Cultured
Dietary Fats adverse effects
Dietary Fats metabolism
Humans
Inflammation immunology
Mice
Mice, Knockout
Myocardium immunology
PPAR delta agonists
PPAR-beta agonists
Thiazoles metabolism
Transcription Factor RelA metabolism
Heart drug effects
Lipids pharmacology
PPAR delta metabolism
PPAR-beta metabolism
Signal Transduction drug effects
Signal Transduction immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1811
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 21070867
- Full Text :
- https://doi.org/10.1016/j.bbalip.2010.11.002