State-of-the-Art Review
Metabolic Origins of Heart Failure

https://doi.org/10.1016/j.jacbts.2016.11.009Get rights and content
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Summary

For more than half a century, metabolic perturbations have been explored in the failing myocardium, highlighting a reversion to a more fetal-like metabolic profile (characterized by depressed fatty acid oxidation and concomitant increased reliance on use of glucose). More recently, alterations in ketone body and amino acid/protein metabolism have been described during heart failure, as well as mitochondrial dysfunction and perturbed metabolic signaling (e.g., acetylation, O-GlcNAcylation). Although numerous mechanisms are likely involved, the current review provides recent advances regarding the metabolic origins of heart failure, and their potential contribution toward contractile dysfunction of the heart.

Key Words

amino acids
fatty acids
glucose
heart failure
ketone bodies

Abbreviations and Acronyms

AA
amino acid
BCAA
branched-chain amino acids
FA
fatty acid
FAO
fatty acid oxidation
GCN2
general control nonderepressible 2
GLOX
glucose oxidation
HBP
hexosamine biosynthesis pathway
HF
heart failure
IR
insulin resistance
LV
left ventricle
MI
myocardial infarction
PTM
post-translational modification
ROS
reactive oxygen species
TauT
taurine transporter

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This work was supported by the U.S. National Institutes of Health grants HL106199, HL074259, HL123574, and HL122974 to Dr. Young and HL111322 and HL133011 to Dr. Wende and American Heart Association grant 16POST270100009 to Dr. McGinnis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.