Evolving Concepts of Myocardial Energy Metabolism
More Than Just Fats and Carbohydrates
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Although mitochondrial fatty acid and carbohydrate oxidation are the major source of ATP production in the heart, it is becoming increasingly clear that oxidation of other energy substrates, such as ketones and branched chain amino acids (BCAAs), can also contribute to energy production. Of importance is that alterations in cardiac ketone and branched chain amino acids metabolism may also impact the severity of heart failure through alterations in cellular signaling, despite these fuels providing a lower contribution to overall energy production.
Dating back to the first studies investigating glucose uptake in the isolated rabbit heart by Locke and Rosenheim in 1907 to the first studies in humans in the late 1940s by Richard Bing and colleagues assessing cardiac substrate extraction via measurement of arterial coronary sinus differences, cardiac energy metabolism has been a topic of interest for cardiologists and scientists alike. The importance of energy metabolism in the heart has become widely appreciated, as has the dynamic nature of the heart’s ability to metabolize a wide range of energy substrates to meet its energy requirements. Fatty acids are recognized as a key source of energy for the heart, as well as carbohydrates, such as glucose and lactate (Figure).1 In 1961, Shipp et al2 were the first to demonstrate that increasing fatty acid availability to the heart results in a marked inhibition of glucose oxidation, though credit for the reciprocal relationship between fatty acids and glucose metabolism (glucose/fatty acid cycle) is attributed to the work of Randle et al.3 Confirmation of Randle’s glucose/fatty acid cycle in the rodent heart has since been demonstrated in the human heart.1