BackgroundCardiomyocytes in postnatal hearts undergo hypertrophy to adapt to increased blood pressure and volume. The process of cardiomyocyte maturation is associated with a cessation from cell cycle and a series of metabolic switches. Prior research has shown metabolic switches in developing mouse hearts. However, metabolic changes in postnatal pig hearts have not been reported.MethodsWe evaluated the metabolic profile in pig hearts at postnatal day 1 (P1), day 3 (P3), day 7 (P7), and day 28 (P28) (n=6 each, both males and females; Yorkshire‐Landrace Cross background) using a targeted liquid chromatography tandem mass spectrometry assay. Expression of lactate dehydrogenase isoforms was evaluated by western blotting.ResultsThere is a clear separation of the detected metabolites in P1 versus P28 hearts. Active anabolisms of nucleotide and proteins were observed in P1 hearts when cardiomyocytes retain high cell cycle activity. Abundance of the intermediate metabolites in the pathways of glycolysis was decreased in P28 comparing to P1 hearts, which implicates an overall reduced level of glycolysis. The decreased abundance of intermediates in TCA cycle and increased abundance of lactic acid in P28 hearts suggested that glycolysis rather than glucose oxidation is the main form of glucose metabolism in mature pig hearts. Reduced abundance of GLCN6P was observed in P28 hearts compared to P1 hearts. Increased abundance of hydroxyproline was observed in P1, P3, and P7 hearts compared to P28 heart.ConclusionPostnatal cardiomyocyte maturation is associated with metabolic switch from glucose to fatty acids, active posttranslational protein modification and ECM remodeling.