Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes

Circ Res. 2013 Aug 16;113(5):603-16. doi: 10.1161/CIRCRESAHA.113.302095.


The network for cardiac fuel metabolism contains intricate sets of interacting pathways that result in both ATP-producing and non-ATP-producing end points for each class of energy substrates. The most salient feature of the network is the metabolic flexibility demonstrated in response to various stimuli, including developmental changes and nutritional status. The heart is also capable of remodeling the metabolic pathways in chronic pathophysiological conditions, which results in modulations of myocardial energetics and contractile function. In a quest to understand the complexity of the cardiac metabolic network, pharmacological and genetic tools have been engaged to manipulate cardiac metabolism in a variety of research models. In concert, a host of therapeutic interventions have been tested clinically to target substrate preference, insulin sensitivity, and mitochondrial function. In addition, the contribution of cellular metabolism to growth, survival, and other signaling pathways through the production of metabolic intermediates has been increasingly noted. In this review, we provide an overview of the cardiac metabolic network and highlight alterations observed in cardiac pathologies as well as strategies used as metabolic therapies in heart failure. Lastly, the ability of metabolic derivatives to intersect growth and survival are also discussed.

Keywords: cardiac metabolism; cardiac pathology; metabolic signaling; metabolic therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological
  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis
  • Autophagy
  • Cardiomegaly / metabolism
  • Cell Survival
  • Diabetes Mellitus / metabolism
  • Diet
  • Energy Metabolism*
  • Fatty Acids / adverse effects
  • Fatty Acids / metabolism
  • Fatty Acids / therapeutic use
  • Heart / growth & development
  • Heart Failure / diet therapy
  • Heart Failure / drug therapy
  • Heart Failure / metabolism
  • Humans
  • Insulin Resistance
  • Metabolic Networks and Pathways / drug effects
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism
  • Myocardial Contraction / physiology*
  • Myocardium / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Obesity / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Randomized Controlled Trials as Topic
  • Substrate Specificity
  • TOR Serine-Threonine Kinases / physiology


  • Fatty Acids
  • Adenosine Triphosphate
  • TOR Serine-Threonine Kinases