Ketones Step to the Plate: A Game Changer for Metabolic Remodeling in Heart Failure?
It is increasingly recognized that metabolic remodeling is integral to heart failure development and progression.1,2 In particular, impairments in the ability of cardiac mitochondria to oxidize fatty acids have been noted along with an increase in glycolysis that is uncoupled from glucose oxidation.3,4 This overall reduction in the myocardial oxidative capacity is purported to be the root cause of energy deficiency in the failing heart. Although past research has primarily focused on myocardial use of glucose and fatty acids, the heart is an omnivore and capable of oxidizing other substrates such as lactate, ketone bodies, and amino acids. The current understanding of the contribution of lactate, ketone bodies, and amino acids to cardiac metabolism is limited, particularly in the setting of heart failure. In this issue of Circulation, two independent studies shed new insights on the reliance of the failing heart on ketone bodies for energy supply. Proteomics analysis in mouse models of heart failure by Aubert et al5 and metabolomics analysis of end-stage human failing hearts by Bedi et al6 demonstrate strong and concordant evidence of increased ketone oxidation in the failing heart.
- Received January 16, 2016.
- Accepted January 21, 2016.