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The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense.

Publication ,  Journal Article
Horton, JL; Davidson, MT; Kurishima, C; Vega, RB; Powers, JC; Matsuura, TR; Petucci, C; Lewandowski, ED; Crawford, PA; Muoio, DM; Recchia, FA ...
Published in: JCI Insight
February 21, 2019

Evidence has emerged that the failing heart increases utilization of ketone bodies. We sought to determine whether this fuel shift is adaptive. Mice rendered incapable of oxidizing the ketone body 3-hydroxybutyrate (3OHB) in the heart exhibited worsened heart failure in response to fasting or a pressure overload/ischemic insult compared with WT controls. Increased delivery of 3OHB ameliorated pathologic cardiac remodeling and dysfunction in mice and in a canine pacing model of progressive heart failure. 3OHB was shown to enhance bioenergetic thermodynamics of isolated mitochondria in the context of limiting levels of fatty acids. These results indicate that the heart utilizes 3OHB as a metabolic stress defense and suggest that strategies aimed at increasing ketone delivery to the heart could prove useful in the treatment of heart failure.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

February 21, 2019

Volume

4

Issue

4

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Thermodynamics
  • Stress, Physiological
  • Oxidation-Reduction
  • Myocardium
  • Mitochondria
  • Mice, Knockout
  • Mice
  • Male
  • Isolated Heart Preparation
 

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Horton, J. L., Davidson, M. T., Kurishima, C., Vega, R. B., Powers, J. C., Matsuura, T. R., … Kelly, D. P. (2019). The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense. JCI Insight, 4(4). https://doi.org/10.1172/jci.insight.124079
Horton, Julie L., Michael T. Davidson, Clara Kurishima, Rick B. Vega, Jeffery C. Powers, Timothy R. Matsuura, Christopher Petucci, et al. “The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense.JCI Insight 4, no. 4 (February 21, 2019). https://doi.org/10.1172/jci.insight.124079.
Horton JL, Davidson MT, Kurishima C, Vega RB, Powers JC, Matsuura TR, et al. The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense. JCI Insight. 2019 Feb 21;4(4).
Horton, Julie L., et al. “The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense.JCI Insight, vol. 4, no. 4, Feb. 2019. Pubmed, doi:10.1172/jci.insight.124079.
Horton JL, Davidson MT, Kurishima C, Vega RB, Powers JC, Matsuura TR, Petucci C, Lewandowski ED, Crawford PA, Muoio DM, Recchia FA, Kelly DP. The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense. JCI Insight. 2019 Feb 21;4(4).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

February 21, 2019

Volume

4

Issue

4

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Thermodynamics
  • Stress, Physiological
  • Oxidation-Reduction
  • Myocardium
  • Mitochondria
  • Mice, Knockout
  • Mice
  • Male
  • Isolated Heart Preparation