| First Author | Finck BN | Year | 2003 |
| Journal | Proc Natl Acad Sci U S A | Volume | 100 |
| Issue | 3 | Pages | 1226-31 |
| PubMed ID | 12552126 | Mgi Jnum | J:81834 |
| Mgi Id | MGI:2450057 | Doi | 10.1073/pnas.0336724100 |
| Citation | Finck BN, et al. (2003) A critical role for PPARalpha -mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation by dietary fat content. Proc Natl Acad Sci U S A 100(3):1226-31 |
| abstractText | To explore the role of peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated derangements in myocardial metabolism in the pathogenesis of diabetic cardiomyopathy, insulinopenic mice with PPARalpha deficiency (PPARalpha(-/-)) or cardiac-restricted overexpression [myosin heavy chain (MHC)-PPAR] were characterized. Whereas PPARalpha(-/-) mice were protected from the development of diabetes-induced cardiac hypertrophy, the combination of diabetes and the MHC-PPAR genotype resulted in a more severe cardiomyopathic phenotype than either did alone. Cardiomyopathy in diabetic MHC-PPAR mice was accompanied by myocardial long-chain triglyceride accumulation. The cardiomyopathic phenotype was exacerbated in MHC-PPAR mice fed a diet enriched in triglyceride containing long-chain fatty acid, an effect that was reversed by discontinuing the high-fat diet and absent in mice given a medium-chain triglyceride-enriched diet. Reactive oxygen intermediates were identified as candidate mediators of cardiomyopathic effects in MHC-PPAR mice. These results link dysregulation of the PPARalpha gene regulatory pathway to cardiac dysfunction in the diabetic and provide a rationale for serum lipid-lowering strategies in the treatment of diabetic cardiomyopathy. |
