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  • Title: Re-balancing cellular energy substrate metabolism to mend the failing heart.
    Author: Glatz JFC, Nabben M, Young ME, Schulze PC, Taegtmeyer H, Luiken JJFP.
    Journal: Biochim Biophys Acta Mol Basis Dis; 2020 May 01; 1866(5):165579. PubMed ID: 31678200.
    Abstract:
    Fatty acids and glucose are the main substrates for myocardial energy provision. Under physiologic conditions, there is a distinct and finely tuned balance between the utilization of these substrates. Using the non-ischemic heart as an example, we discuss that upon stress this substrate balance is upset resulting in an over-reliance on either fatty acids or glucose, and that chronic fuel shifts towards a single type of substrate appear to be linked with cardiac dysfunction. These observations suggest that interventions aimed at re-balancing a tilted substrate preference towards an appropriate mix of substrates may result in restoration of cardiac contractile performance. Examples of manipulating cellular substrate uptake as a means to re-balance fuel supply, being associated with mended cardiac function underscore this concept. We also address the molecular mechanisms underlying the apparent need for a fatty acid-glucose fuel balance. We propose that re-balancing cellular fuel supply, in particular with respect to fatty acids and glucose, may be an effective strategy to treat the failing heart.
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