Figure 1.

Contribution of different substrates to ATP production during cardiac development and disease progression. The heart is capable of using all classes of substrates, including carbohydrates, lipids, amino acids and ketone bodies to meet its energetic demands. Its substrate preference changes throughout the life cycle as well as under physiological and pathological conditions, which allows the heart to adapt to environmental changes. (A) The developing heart is highly dependent on aerobic glycolysis and lactate oxidation, while oxidation of fatty acids plays only a minor role. This metabolic phenotype is well suited for the biosynthesis of cellular building blocks, which are necessary for cardiomyocyte proliferation and cellular growth. (B) The adult heart is exposed to an increased haemodynamic load and oxygen tension. It mainly uses oxidative metabolism for ATP production, which is reflected by a substantial increase in mitochondrial volume mass. Fatty acids become the predominant fuel for the adult hearts. (C) Hearts with pathological hypertrophy revert to a foetal metabolic profile, demonstrating increased reliance on glucose and reduced oxidative capacity. In advanced heart failure, increased use of ketone bodies as fuel has been suggested.