Multi-omics Approach Reveals Metabolic Changes in the Heart at Birth

During late gestation, the fetal heart relies primarily on glucose and lactate to support rapid growth and development. While numerous studies describe changes in heart metabolism a few weeks after birth to preferentially utilize fatty acids, little is known about metabolic changes of the heart within the first day of life. Therefore, we used the ovine model of pregnancy to investigate metabolic differences between the near-term fetal and the newborn heart. We observed greater abundance of metabolites involved in butanoate and propanoate metabolism, and glycolysis/gluconeogenesis in the term fetal heart (FDR-corrected p<0.10) and differential expression in these pathways were confirmed with single-sample gene set enrichment analysis (ssGSEA) (FDR-corrected p<0.05). Immediately following birth, newborn hearts displayed enrichment in purine, fatty acid, and glycerophospholipid metabolic pathways, as well as oxidative phosphorylation with significant alterations in lipids and metabolites to support transcriptomic findings. While other studies suggest a switch from carbohydrate metabolism to fatty acid metabolism in the neonatal heart in as early as 2 weeks following birth, our data show that this metabolic switch in the heart begins by the first day of postnatal life. A better understanding of metabolic alterations that occur in the heart following birth may improve treatment of neonates at risk for heart failure. Samples were collected for metabolomics, lipidomic, and transcriptomic approaches from the left and right ventricles and intraventricular septum in 7 fetuses at gestational day 142 and 7 newborn lambs on the day of birth.