Maturation of Lipid Metabolism in the Fetal and Newborn Sheep Heart

Am J Physiol Regul Integr Comp Physiol. 2023 Oct 23. doi: 10.1152/ajpregu.00122.2023. Online ahead of print.ABSTRACTAt birth, the fetus experiences a dramatic change in environment which is accompanied by a shift in myocardial fuel preference from lactate and glucose in fetal life to fatty acid oxidation after birth. We hypothesized that fatty acid metabolic machinery would mature during fetal life in preparation for this extreme metabolic transformation at birth. We quantified the pre- (94-day and 135-day gestation, term ~147 days) and post-natal (5±4 days postnatal) gene expression and protein levels for fatty acid transporters and enzymes in hearts from a precocial species, the sheep. Gene expression of CD36, ACSL1, CPT1, HADH, ACAT1, IDH and GPAT progressively increased through the perinatal period whereas several genes FATP6, ACSL3, LCAD, VLCAD, PDK4, PAP and DGAT were stable in fetal hearts and had high expression after birth. Protein expression of CD36 and ACSL1 progressively increased throughout the perinatal period, while CPT1a decreased and CPT1b remained constitutively expressed. Using fluorescent-tagged long chain fatty acids (BODIPY C12), we demonstrated that fetal (125±1 days gestation) cardiomyocytes produce 59% larger lipid droplets (p<0.05) compared to newborn (8±1 day) cardiomyocytes. These results provide novel insights into the perinatal maturation of cardiac fatty acid metabolism in a precocial species.PMID:37867472 | DOI:10.1152/ajpregu.00122.2023
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Source Type: research