| First Author | Alvarez-Guardia D | Year | 2011 |
| Journal | Biochim Biophys Acta | Volume | 1811 |
| Issue | 2 | Pages | 59-67 |
| PubMed ID | 21070867 | Mgi Jnum | J:170276 |
| Mgi Id | MGI:4946169 | Doi | 10.1016/j.bbalip.2010.11.002 |
| Citation | Alvarez-Guardia D, et al. (2011) PPARbeta/delta activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells. Biochim Biophys Acta 1811(2):59-67 |
| abstractText | 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-kappaB (NF-kappaB), 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-kappaB. Since PPARbeta/delta is the most prevalent PPAR isoform in the heart, we analyzed the effects of the PPARbeta/delta agonist GW501516 on inflammatory parameters. A high-fat diet induced the expression of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and interleukin-6, and enhanced the activity of NF-kappaB 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. PPARbeta/delta activation by GW501516 enhanced the physical interaction between PPARbeta/delta and p65, which suggests that this mechanism may also interfere NF-kappaB transactivation capacity in the heart. GW501516-induced PPARbeta/delta 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 PPARbeta/delta has been postulated as a potential target in the treatment of obesity and the insulin resistance state. |
