Preparing your results

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The cardiac phenotype induced by PPARalpha 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 glucose uptake and oxidation decreased in MHC-PPAR mice, a metabolic phenotype strikingly similar to that of the diabetic heart. MHC-PPAR hearts exhibited signatures of diabetic cardiomyopathy including ventricular hypertrophy, activation of gene markers of pathologic hypertrophic growth, and transgene expression-dependent alteration in systolic ventricular dysfunction. These results demonstrate that (a) PPARalpha is a critical regulator of myocardial fatty acid uptake and utilization, (b) activation of cardiac PPARalpha regulatory pathways results in a reciprocal repression of glucose uptake and utilization pathways, and (c) derangements in myocardial energy metabolism typical of the diabetic heart can become maladaptive, leading to cardiomyopathy.

Pubmed ID: 11781357


  • Finck BN
  • Lehman JJ
  • Leone TC
  • Welch MJ
  • Bennett MJ
  • Kovacs A
  • Han X
  • Gross RW
  • Kozak R
  • Lopaschuk GD
  • Kelly DP


The Journal of clinical investigation

Publication Data

January 8, 2002

Associated Grants

  • Agency: NHLBI NIH HHS, Id: F32 HL67575
  • Agency: PHS HHS, Id: JDFI 996003
  • Agency: NHLBI NIH HHS, Id: P01 HL13851
  • Agency: NHLBI NIH HHS, Id: P01 HL5727805
  • Agency: NIDDK NIH HHS, Id: P30 DK52574
  • Agency: NIDDK NIH HHS, Id: P30 DK56341
  • Agency: NIDDK NIH HHS, Id: R01 DK45416

Mesh Terms

  • Animals
  • Cardiomegaly
  • Cardiomyopathies
  • Carrier Proteins
  • Diabetes Mellitus, Experimental
  • Energy Metabolism
  • Fatty Acids
  • Female
  • Gene Expression
  • Glucose
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Myocardium
  • Phenotype
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Leptin
  • Transcription Factors