Ketone Body Metabolism in the Ischemic Heart

Abstract

Ketone bodies have been identified as an important, alternative fuel source in heart failure. In addition, the use of ketone bodies as a fuel source has been suggested to be a potential ergogenic aid for endurance exercise performance. These findings have certainly renewed interest in the use of ketogenic diets and exogenous supplementation in an effort to improve overall health and disease. However, given the prevalence of ischemic heart disease and myocardial infarctions, these strategies may not be ideal for individuals with coronary artery disease. Although research studies have clearly defined changes in fatty acid and glucose metabolism during ischemia and reperfusion, the role of ketone body metabolism in the ischemic and reperfused myocardium is less clear. This review will provide an overview of ketone body metabolism, including the induction of ketosis via physiological or nutritional strategies. In addition, the contribution of ketone body metabolism in healthy and diseased states, with a particular emphasis on ischemia-reperfusion (I-R) injury will be discussed.

Impact of Prenatal Exposure to Maternal Diabetes and High-Fat Diet on Postnatal Myocardial Ketone Body Metabolism in Rats

“…Ketones produce ATP more efficiently than glucose or fatty acid and recent studies suggest that the failing heart benefits from ketone bodies as an energy source [ 16 , 21 ]. βHOB, acetoacetate, and acetone are the three primary ketones in circulation, whereas βHOB is found in the highest levels [ 15 , 35 ]. Ketone bodies are products of fatty acid oxidation.…”

Ketogenic Diet and Cardiac Substrate Metabolism

“…The heart is often described as a metabolic omnivore since it readily utilizes all energy substrates as fuel and easily flexes between different compositions of energy substrates depending on energy demand and substrate availability ( Figure 1 ). In the healthy, postabsorptive heart, fatty acids account for around 70% of cardiac energy consumption [ 19 , 20 ], whereas glucose and ketone bodies have been estimated to deliver less than 10% of the total energy demand [ 21 ]. Even this modest contribution from glucose and ketone bodies may be an overestimation, as evidenced by a recent elegant metabolomics’ study, in which glucose uptake was barely measurable and was estimated to account for less than 1% of total energy demand [ 22 ].…”

“…Even this modest contribution from glucose and ketone bodies may be an overestimation, as evidenced by a recent elegant metabolomics’ study, in which glucose uptake was barely measurable and was estimated to account for less than 1% of total energy demand [ 22 ]. The remaining myocardial energy need is derived from oxidation of lactate and branched-chain amino acids [ 21 , 23 ]. Glucose, fatty acids, ketone bodies, and branched-chain amino acids are, thus, all sources of acetyl-CoA feeding into the Krebs cycle [ 14 ] ultimately generating ATP.…”

“…As a consequence of the reduced ATP production by glucose oxidation, glycolytic processes are frequently upregulated, particularly evident in ischemic heart failure [ 29 ]. Moreover, fatty acid oxidation is decreased in tandem with the increase in glycolysis [ 21 ]. In this setting, it is becoming increasingly clear that the failing heart may rely much more on ketone bodies as a source of energy than the healthy heart [ 23 , 30 ].…”

A review of potential mechanisms and uses of SGLT2 inhibitors in ischemia-reperfusion phenomena

“…However, these contradictory results, well summarized in Kolwicz and al. review[ 65 ], only raise the need for additional studies at the metabolic level.…”