Metabolic Changes In Heart Research Articles

Multiomics approach reveals metabolic changes in the heart at birth.

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.

Metabolic adjustments of an air‐breathing teleost, Channa maculata, to acute and prolonged exposure to hypoxic water

Plasma and tissue metabolite levels were measured in the air‐breathing Channa maculata during acute and prolonged exposure to normoxic and hypoxic water. Exposure of the fish to hypoxic water (water oxygen partial pressure, PwO2= 50 mmHg) for 1 h caused increases in plasma glucose and lactate, liver and brain lactate, liver a‐amino acid, heart and brain alanine and brain succinate levels. The metabolic changes in heart, brain and muscle could only be detected when PwO2 was 30 or 10 mmHg. Heart glycogen and liver lipid decreased during acute exposure. Prolonged exposure to hypoxic water (PwO2= 30 mmHg) for 3 days caused an increase in plasma glycerol and liver lactate dehydrogenase activity, and a depletion of glycogen store in all tissues investigated. However, metabolite levels which had been elevated during acute hypoxic exposure were observed to return to their normoxic values after prolonged exposure. It was concluded that anaerobic metabolism was triggered by acute exposure to hypoxic water. Prolonged exposure to hypoxic water induced a metabolic readjustment involving mobilisation of lipid and glycogen stores, which is probably a reflection of the high metabolic load of aerial respiration imposed on the fish during exposure to hypoxic water.

Stimulation of phosphorylation and inactivation of pyruvate dehydrogenase by physiological inhibitors of the pyruvate dehydrogenase reaction

OXIDATION of pyruvate in perfused rat heart is inhibited by diabetes and by oxidation of fatty acids and ketone bodies1. Enhanced release and oxidation of fatty acids from muscle glycerides may be an important factor in the effects of diabetes2–4. These effects on pyruvate oxidation have generally been attributed to inhibition of pyruvate dehydrogenase, and regulation of this enzyme is considered to be of crucial importance in the selection of fuels for respiration and in the metabolic changes in heart and other tissues in diabetes and starvation.