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INNOSC Theranostics and
Pharmacological Sciences Cardiac metabolism in health and disease

Table 1. Substrate utilization for ATP production in cardiac metabolism across health and disease states
Conditions Substrates References
Fatty acid Glucose Alternative substrates
Normal heart 70% of total ATP production 25% of total ATP production 5% of total ATP production 1,2
Obesity Increase Decrease Decrease 8-12
Diabetes mellitus Increase Decrease Decrease 8-12
Ischemic heart Decrease Increase Increase 8-12
Reperfusion heart Increase Decrease Decrease 8-12
Cardiac hypertrophy Decrease Increase Increase 5-7
Heart failure Decrease Increase Increase 5-7
Notes: “Increase” signifies an increase exceeding a certain percentage from the normal condition; “Decrease” signifies a decrease exceeding a certain
percentage from the normal condition.
Abbreviation: ATP: Adenosine triphosphate.

states. Central to this paradigm are the intersecting Future strides in understanding cardiac metabolism
pathways of mitochondrial FAO, glycolysis, and glucose entail elucidating regulatory mechanisms governing
utilization, which establish the energetic framework of substrate preferences, exploring the “Randle cycle,”
a healthy heart. However, in pathological conditions, a and probing the molecular intricacies in disease states.
3,4
noticeable divergence emerges: while cardiac hypertrophy Integrating diverse disciplines encompassing metabolomics,
and heart failure exhibit adaptations favoring more oxygen- genetics, and systems biology with clinical data can facilitate
efficient substrates such as glycolysis or ketone bodies, tailored interventions and innovative diagnostic tools,
conditions such as obesity, diabetes, and DCM showcase revolutionizing cardiovascular medicine. Collaborative
heightened mitochondrial FAO. This juxtaposition efforts leveraging advanced technologies promise to reshape
underscores the complex interplay between substrate the landscape of cardiac disease management by providing
preferences and energy pathways, epitomizing the nuanced deeper insights into metabolic regulation in the heart.
metabolic shifts characterizing cardiac pathology.
Hormonal imbalances, mitochondrial irregularities, and 10. Conclusion
enzymatic disruptions add layers of complexity to cardiac Understanding the profound impact of metabolic disorders
metabolism in disease states. Diverse research perspectives and heart diseases on myocardial metabolism is crucial,
propose varying degrees of reliance on glycolysis, as these conditions influence various facets such as energy
alternative substrates, or increased mitochondrial FAO, demand, substrate utilization, and cardiac mitochondrial
presenting a mosaic of hypotheses. The exploration of function. These factors intricately regulate cardiac energy
these intricate pathways offers a multitude of potential metabolism and efficiency. Unraveling the molecular
therapeutic targets for understanding and intervening in mechanisms behind these metabolic alterations during such
metabolic dysregulation in various cardiac diseases. 13-15 conditions holds promise in refining therapeutic strategies
and pinpointing targets to treat heart diseases while
The “Randle cycle” concept, elucidating the reciprocal bolstering cardiac efficiency. A schematic representation
relationship between mitochondrial FAO and glycolysis, of substrate utilization for ATP production in cardiac
governs substrate utilization within the cardiac milieu. metabolism across both healthy and diseased conditions
The adaptability of the heart during myocardial ischemia is depicted in Table 1. Despite the potential benefits of
and reperfusion, adjusting substrate preferences based modulating cardiac metabolism to enhance heart function,
on oxygen availability, emphasizes the dynamic nature of the intricate links between metabolic alterations and
cardiac metabolism under stress. 11 pathological conditions remain poorly elucidated. Clinical
The divergence between adaptive responses favoring efforts to intervene and modulate cardiac metabolism have
glucose oxidation and heightened mitochondrial FAO in not provided comprehensive insights into this domain.
cardiac hypertrophy and heart failure necessitates further Therefore, future investigations should aim at deeper
investigation to comprehend its impact on compromised exploration, unraveling the intricate molecular changes,
cardiac energetics. Addressing this discrepancy is pivotal genetic mutations, and complex networks involved in
for understanding and mitigating metabolic dysregulation altering cardiac energy metabolism. Advancements
in diseased hearts. in understanding these mechanisms hold the key to

Volume 7 Issue 2 (2024) 6 doi: 10.36922/itps.2302