Re-balancing cellular energy substrate metabolism to mend the failing heart

Publication date: Available online 31 October 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jan F.C. Glatz, Miranda Nabben, Martin E. Young, P. Christian Schulze, Heinrich Taegtmeyer, Joost J.F.P. LuikenAbstractFatty 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.

Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 31, 2019 Category: Molecular Biology Source Type: research