| First Author | Barbieri M | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 4 | Pages | e35999 |
| PubMed ID | 22563432 | Mgi Jnum | J:225004 |
| Mgi Id | MGI:5689956 | Doi | 10.1371/journal.pone.0035999 |
| Citation | Barbieri M, et al. (2012) Effects of PPARs agonists on cardiac metabolism in littermate and cardiomyocyte-specific PPAR-gamma-knockout (CM-PGKO) mice. PLoS One 7(4):e35999 |
| abstractText | Understanding the molecular regulatory mechanisms controlling for myocardial lipid metabolism is of critical importance for the development of new therapeutic strategies for heart diseases. The role of PPARgamma and thiazolidinediones in regulation of myocardial lipid metabolism is controversial. The aim of our study was to assess the role of PPARgamma on myocardial lipid metabolism and function and differentiate local/from systemic actions of PPARs agonists using cardiomyocyte-specific PPARgamma -knockout (CM-PGKO) mice. To this aim, the effect of PPARgamma, PPARgamma/PPARalpha and PPARalpha agonists on cardiac function, intra-myocyte lipid accumulation and myocardial expression profile of genes and proteins, affecting lipid oxidation, uptake, synthesis, and storage (CD36, CPT1MIIA, AOX, FAS, SREBP1-c and ADPR) was evaluated in cardiomyocyte-specific PPARgamma-knockout (CM-PGKO) and littermate control mice undergoing standard and high fat diet (HFD). At baseline, protein levels and mRNA expression of genes involved in lipid uptake, oxidation, synthesis, and accumulation of CM-PGKO mice were not significantly different from those of their littermate controls. At baseline, no difference in myocardial lipid content was found between CM-PGKO and littermate controls. In standard condition, pioglitazone and rosiglitazone do not affect myocardial metabolism while, fenofibrate treatment significantly increased CD36 and CPT1MIIA gene expression. In both CM-PGKO and control mice submitted to HFD, six weeks of treatment with rosiglitazone, fenofibrate and pioglitazone lowered myocardial lipid accumulation shifting myocardial substrate utilization towards greater contribution of glucose. In conclusion, at baseline, PPARgamma does not play a crucial role in regulating cardiac metabolism in mice, probably due to its low myocardial expression. PPARs agonists, indirectly protect myocardium from lipotoxic damage likely reducing fatty acids delivery to the heart through the actions on adipose tissue. Nevertheless a direct non-PPARgamma mediated mechanism of PPARgamma agonist could not be ruled out. |
