Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure

Circ Heart Fail. 2010 May;3(3):420-30. doi: 10.1161/CIRCHEARTFAILURE.109.888479. Epub 2010 Feb 22.


Background: Congestive heart failure (CHF) is associated with a change in cardiac energy metabolism. However, the mechanism by which this change is induced and causes the progression of CHF is unclear.

Methods and results: We analyzed the cardiac energy metabolism of Dahl salt-sensitive rats fed a high-salt diet, which showed a distinct transition from compensated left ventricular hypertrophy to CHF. Glucose uptake increased at the left ventricular hypertrophy stage, and glucose uptake further increased and fatty acid uptake decreased at the CHF stage. The gene expression related to glycolysis, fatty acid oxidation, and mitochondrial function was preserved at the left ventricular hypertrophy stage but decreased at the CHF stage and was associated with decreases in levels of transcriptional regulators. In a comprehensive metabolome analysis, the pentose phosphate pathway that regulates the cellular redox state was found to be activated at the CHF stage. Dichloroacetate (DCA), a compound known to enhance glucose oxidation, increased energy reserves and glucose uptake. DCA improved cardiac function and the survival of the animals. DCA activated the pentose phosphate pathway in the rat heart. DCA activated the pentose phosphate pathway, decreased oxidative stress, and prevented cell death of cultured cardiomyocytes.

Conclusions: Left ventricular hypertrophy or CHF is associated with a distinct change in the metabolic profile of the heart. DCA attenuated the transition associated with increased energy reserves, activation of the pentose phosphate pathway, and reduced oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dichloroacetic Acid / therapeutic use
  • Disease Models, Animal
  • Energy Metabolism / physiology*
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Heart Failure / drug therapy
  • Heart Failure / etiology*
  • Heart Failure / metabolism*
  • Hypertrophy, Left Ventricular / complications*
  • Hypertrophy, Left Ventricular / drug therapy
  • Hypertrophy, Left Ventricular / metabolism*
  • Male
  • Metabolome / physiology
  • Rats
  • Rats, Inbred Dahl
  • Ventricular Remodeling / physiology*


  • Fatty Acids
  • Dichloroacetic Acid
  • Glucose