Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1866, Issue 5, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2019.165579
Keywords
Long-chain fatty acids; Glucose; Energy homeostasis; Substrate balance; Cardiac contractile function; Heart failure; Diabetes
Funding
- VENI Innovational Research Grant from the Netherlands Organisation for Scientific Research (ZonMw-NWO grant) [916.14.050]
- NIH [HL106199, HL074259, HL123574]
- NHLBI [HL 61483, HL 123627]
- Cancer Prevention and Research Institute of Texas (CPRIT)
- NHLBI
- Else Kroner-Fresenius Foundation
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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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