Multiomics approach reveals metabolic changes in the heart at birth

Abstract

During late gestation, the fetal heart primarily relies on glucose and lactate to support rapid growth and development. Although numerous studies describe changes in heart metabolism to utilize fatty acids preferentially a few weeks after birth, little is known about metabolic changes of the heart within the first day following birth. Therefore, we used the ovine model of pregnancy to investigate metabolic differences between the near-term fetal and the newborn heart. Heart tissue was collected for metabolomic, 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. Significant metabolites and lipids were identified using a Student’s t-test, whereas differentially expressed genes were identified using a moderated t-test with empirical Bayes method [false discovery rate (FDR)-corrected P < 0.10]. Single-sample gene set enrichment analysis (ssGSEA) was used to identify pathways enriched on a transcriptomic level (FDR-corrected P < 0.05), whereas overrepresentation enrichment analysis was used to identify pathways enriched on a metabolomic level ( P < 0.05). We observed greater abundance of metabolites involved in butanoate and propanoate metabolism, and glycolysis in the term fetal heart and differential expression in these pathways were confirmed with ssGSEA. Immediately following birth, newborn hearts displayed enrichment in purine, fatty acid, and glycerophospholipid metabolic pathways as well as oxidative phosphorylation with significant alterations in both lipids and metabolites to support transcriptomic findings. A better understanding of metabolic alterations that occur in the heart following birth may improve treatment of neonates at risk for heart failure.