The Failing Heart Relies on Ketone Bodies as a Fuel
By G. Aubert, Ola J. Martin, J. Horton, Ling Lai, Rick B. Vega, T. Leone, T. Koves, S. Gardell, M. Krüger, C. Hoppel and 4 more. Circulation, 2016
630 citations recorded by the source corpus.
Background— Significant evidence indicates that the failing heart is energy starved. During the development of heart failure, the capacity of the heart to utilize fatty acids, the chief fuel, is diminished. Identification of alternate pathways for myocardial fuel oxidation could unveil novel strategies to treat heart failure. Methods and Results— Quantitative mitochondrial proteomics was used to identify energy metabolic derangements that occur during the development of cardiac hypertrophy and heart failure in well-defined mouse models. As expected, the amounts of proteins involved in fatty acid utilization were downregulated in myocardial samples from the failing heart. Conversely, expression of &bgr;-hydroxybutyrate dehydrogenase 1, a key enzyme in the ketone oxidation pathway, was increased in the heart failure samples. Studies of relative oxidation in an isolated heart preparation using ex vivo nuclear magnetic resonance combined with targeted quantitative myocardial metabolomic profiling using mass spectrometry revealed that the hypertrophied and failing heart shifts to oxidizing ketone bodies as a fuel source in the context of reduced capacity to oxidize fatty acids. Distinct myocardial metabolomic signatures of ketone oxidation were identified. Conclusions— These results indicate that the hypertrophied and failing heart shifts to ketone bodies as a significant fuel source for oxidative ATP production. Specific metabolite biosignatures of in vivo cardiac ketone utilization were identified. Future studies aimed at determining whether this fuel shift is adaptive or maladaptive could unveil new therapeutic strategies for heart failure.
Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/1754fab5c1ca4f2919e6726b54cdfa80cd9f6be3
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Citations in the corpus
- Association between insulin resistance and the development of cardiovascular disease (2018, background): “In this situation, the heart uses alternative pathways such as ketone bodies as fuel for oxidative ATP production [166].”
- CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis (2016, neutral): “, b-hydroxybutyrate dehydrogenase) are increased (56).”