Metabolic flexibility of mitochondria plays a key role in balancing glucose and fatty acid metabolism in the diabetic heart

In order to meet its energy requirements, the heart has the intrinsic capability to metabolize a wide range of energy substrates. In normal conditions, the heart favors fatty acids as the main energetic substrate, followed by carbohydrates, ketone bodies, and, lastly, amino acids (1,2). Yet, the myocardium is able to dynamically switch its metabolism according to substrate availability, in order to attempt to guarantee an efficient pumping function in virtually any scenario (2,3). Mechanistically, this phenomenon seems to be possible, as the different substrates available in the heart compete as source of energy, making the final choice essentially based on the relative substrate concentrations. In a seminal Nature article published in 1961, Schipp et al. (4) demonstrated for the first time that increasing fatty acid availability resulted in a marked inhibition of glucose oxidation.