Maturation of Cardiac Energy Metabolism During Perinatal Development

Abstract

As one of the highest energy consumer organ in mammals, the heart has to be provided with a high amount of energy as soon as its first beats in utero. During the development of this organ, energy is produced within the cardiac muscle cell depending on substrate availability, oxygen pressure and cardiac workload that drastically change at birth. Thus, energy metabolism relying essentially on carbohydrates in fetal heart is very different from the adult one and birth is the trigger of a profound maturation which ensures the transition to a highly oxidative metabolism depending on lipid utilization. To face the substantial increase in cardiac workload resulting from the growth of the organism during the postnatal period, the heart not only develops its capacity for energy production but also undergoes a hypertrophic growth to adapt its contractile capacity to its new function. This leads to a profound cytoarchitectural remodeling of the cardiomyocyte which becomes a highly compartmentalized structure. As a consequence, within the mature cardiac muscle, energy transfer between energy producing and consuming compartments requires organized energy transfer systems that are established in the early postnatal life. This review aims at describing the major rearrangements of energy metabolism during the perinatal development.

Cardiomyocyte proliferation, a target for cardiac regeneration

“…To support these hemodynamic changes, profound cellular remodeling including maturation and hypertrophy of cardiomyocytes is essential [46]. These postnatal cellular changes require high energy production which will be provided by major rearrangements of energy metabolism switching from anaerobic glycolysis to oxygen-dependent mitochondrial oxidative phosphorylation [47] (Fig. 1).…”

Glucocorticoid Receptor ablation promotes cardiac regeneration by hampering cardiomyocyte terminal differentiation

“…Beginning in late gestation and continuing through the first weeks after birth, cardiomyocytes undergo an important transition from anaerobic glycolysis in the cytosol to oxidative metabolism in mitochondria, which is dependent on lipid utilization 27,28 . This transition is part of the establishment of more efficient energy production systems, to face the substantial increase in cardiac workload resulting from the growth of the organism 28,29 .…”

“…During the early postnatal development, the cytoarchitectural structure of cardiomyocytes shifts from loose spatial organization to highly organized and more efficient sarcomere units 28,30 . To evaluate a potential impact of GR ablation on this physiological reorganization, we performed ultrastructure analysis by transmission electron microscopy of GR-cKO and control cardiomyocytes at birth and during the early postnatal development.…”

Mitochondrial functional resilience after TFAM ablation in adult cardiomyocytes

“…A possible explanation for these differences-early and rapid onset of cardiomyopathy and shortened lifespan in embryonic/postnatal mice, versus functional resilience and slow disease onset in adult-is the inherent differences between these two stages: the embryonic/postnatal heart is a developing tissue undergoing active growth and proliferation, while the adult heart is terminally differentiated. Metabolic requirements, mitochondrial function, and even mitochondrial morphology differ between these two states-with the more fragmented mitochondria of the developing cardiomyocytes maturing into a highly interconnected reticulum of the differentiated cardiomyocytes, (28,39,40). Moreover, TFAM may have a critical role in cardiomyocyte proliferation (22).…”

“…During this period, cardiac mitochondria also undergo a profound structural and functional maturation, with the fragmented mitochondria of embryonic and early postnatal cardiomyocytes developing into the interconnected network of adult cardiomyocytes (27). This transition is marked by increase mitochondrial biogenesis and a metabolic shift toward b-oxidation (27,28). The fully differentiated adult heart could therefore have different needs for mtDNA maintenance, but this question has not been investigated.…”