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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Horton, JL; Davidson, MT; Kurishima, C; Vega, RB; Powers, JC; Matsuura, TR; Petucci, C; Lewandowski, ED; Crawford, PA; Muoio, DM; Recchia, FA; Kelly, DP

Published Date

  • February 21, 2019

Published In

Volume / Issue

  • 4 / 4

PubMed ID

  • 30668551

Pubmed Central ID

  • 30668551

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.124079

Language

  • eng

Conference Location

  • United States