title: Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kato
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Niizuma
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Inuzuka
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Kawashima
authors.forename: Junji
authors.initials: J
authors.lastname: Okuda
authors.forename: Yodo
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: Michiko
authors.initials: M
authors.lastname: Narazaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuda
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shioi
mesh_terms: D000818:Animals; D003999:Dichloroacetic Acid / Q000627:therapeutic use; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000502:physiology; D051381:Rats; D020303:Rats, Inbred Dahl; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D005227:Fatty Acids; D003999:Dichloroacetic Acid; D005947:Glucose