The Failing Heart Relies on Ketone Bodies as a Fuel

DOI Web Site 被引用文献24件
  • Gregory Aubert
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Ola J. Martin
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Julie L. Horton
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Ling Lai
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Rick B. Vega
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Teresa C. Leone
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Timothy Koves
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Stephen J. Gardell
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Marcus Krüger
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Charles L. Hoppel
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • E. Douglas Lewandowski
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Peter A. Crawford
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Deborah M. Muoio
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...
  • Daniel P. Kelly
    From Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL (G.A., O.J.M., J.L.H., L.L., R.B.V., T.C.L., S.J.G., P.A.C., D.P.K.); Departments of Medicine, Pharmacology, and Cancer Biology, Duke University, Durham, NC (T.K., D.M.M.); CECAD Research Center, Institute for Genetics, University of Cologne, Cologne, Germany (M.K.); Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, OH (C.L.H.); College of Medicine, University...

説明

<jats:sec> <jats:title>Background—</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p>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 β-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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>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.</jats:p> </jats:sec>

収録刊行物

  • Circulation

    Circulation 133 (8), 698-705, 2016-02-23

    Ovid Technologies (Wolters Kluwer Health)

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