The cardiac phenotype induced by PPARα overexpression mimics that caused by diabetes mellitus

Recent evidence has defined an important role for PPARalpha in the transcriptional control of cardiac energy metabolism. To investigate the role of PPARalpha in the genesis of the metabolic and functional derangements of diabetic cardiomyopathy, mice with cardiac-restricted overexpression of PPARalpha (MHC-PPAR) were produced and characterized. The expression of PPARalpha target genes involved in cardiac fatty acid uptake and oxidation pathways was increased in MHC-PPAR mice. Surprisingly, the expression of genes involved in glucose transport and utilization was reciprocally repressed in MHC-PPAR hearts. Consistent with the gene expression profile, myocardial fatty acid oxidation rates were increased and…

• NI
  National Institutes of Health

  Awards: DK56341, PO1 HL, DK52574, P30 DK52574, (NIH), HL57278, P30 DK, P30 DK56341
• NH
  National Heart, Lung, and Blood Institute