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Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency.

Publication ,  Journal Article
Ho, KL; Zhang, L; Wagg, C; Al Batran, R; Gopal, K; Levasseur, J; Leone, T; Dyck, JRB; Ussher, JR; Muoio, DM; Kelly, DP; Lopaschuk, GD
Published in: Cardiovasc Res
September 1, 2019

AIMS: The failing heart is energy-starved and inefficient due to perturbations in energy metabolism. Although ketone oxidation has been shown recently to increase in the failing heart, it remains unknown whether this improves cardiac energy production or efficiency. We therefore assessed cardiac metabolism in failing hearts and determined whether increasing ketone oxidation improves cardiac energy production and efficiency. METHODS AND RESULTS: C57BL/6J mice underwent sham or transverse aortic constriction (TAC) surgery to induce pressure overload hypertrophy over 4-weeks. Isolated working hearts from these mice were perfused with radiolabelled β-hydroxybutyrate (βOHB), glucose, or palmitate to assess cardiac metabolism. Ejection fraction decreased by 45% in TAC mice. Failing hearts had decreased glucose oxidation while palmitate oxidation remained unchanged, resulting in a 35% decrease in energy production. Increasing βOHB levels from 0.2 to 0.6 mM increased ketone oxidation rates from 251 ± 24 to 834 ± 116 nmol·g dry wt-1 · min-1 in TAC hearts, rates which were significantly increased compared to sham hearts and occurred without decreasing glycolysis, glucose, or palmitate oxidation rates. Therefore, the contribution of ketones to energy production in TAC hearts increased to 18% and total energy production increased by 23%. Interestingly, glucose oxidation, in parallel with total ATP production, was also significantly upregulated in hearts upon increasing βOHB levels. However, while overall energy production increased, cardiac efficiency was not improved. CONCLUSIONS: Increasing ketone oxidation rates in failing hearts increases overall energy production without compromising glucose or fatty acid metabolism, albeit without increasing cardiac efficiency.

Duke Scholars

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Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

September 1, 2019

Volume

115

Issue

11

Start / End Page

1606 / 1616

Location

England

Related Subject Headings

  • Ventricular Function, Left
  • Stroke Volume
  • Oxidation-Reduction
  • Myocardium
  • Mice, Inbred C57BL
  • Male
  • Hypertrophy, Left Ventricular
  • Heart Failure
  • Glucose
  • Fatty Acids
 

Citation

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Ho, K. L., Zhang, L., Wagg, C., Al Batran, R., Gopal, K., Levasseur, J., … Lopaschuk, G. D. (2019). Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency. Cardiovasc Res, 115(11), 1606–1616. https://doi.org/10.1093/cvr/cvz045
Ho, Kim L., Liyan Zhang, Cory Wagg, Rami Al Batran, Keshav Gopal, Jody Levasseur, Teresa Leone, et al. “Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency.Cardiovasc Res 115, no. 11 (September 1, 2019): 1606–16. https://doi.org/10.1093/cvr/cvz045.
Ho KL, Zhang L, Wagg C, Al Batran R, Gopal K, Levasseur J, et al. Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency. Cardiovasc Res. 2019 Sep 1;115(11):1606–16.
Ho, Kim L., et al. “Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency.Cardiovasc Res, vol. 115, no. 11, Sept. 2019, pp. 1606–16. Pubmed, doi:10.1093/cvr/cvz045.
Ho KL, Zhang L, Wagg C, Al Batran R, Gopal K, Levasseur J, Leone T, Dyck JRB, Ussher JR, Muoio DM, Kelly DP, Lopaschuk GD. Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency. Cardiovasc Res. 2019 Sep 1;115(11):1606–1616.
Journal cover image

Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

September 1, 2019

Volume

115

Issue

11

Start / End Page

1606 / 1616

Location

England

Related Subject Headings

  • Ventricular Function, Left
  • Stroke Volume
  • Oxidation-Reduction
  • Myocardium
  • Mice, Inbred C57BL
  • Male
  • Hypertrophy, Left Ventricular
  • Heart Failure
  • Glucose
  • Fatty Acids