Maturation of lipid metabolism in the fetal and newborn sheep heart.

At birth, the fetus experiences a dramatic change in environment that 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 postnatal (5 ± 4 days postnatal) gene expression and protein levels for fatty acid transporters and enzymes in hearts from a precocial species, the sheep.

Intrauterine growth restriction elevates circulating acylcarnitines and suppresses fatty acid metabolism genes in the fetal sheep heart.

At birth, the mammalian myocardium switches from using carbohydrates as the primary energy substrate to free fatty acids as the primary fuel. Thus, a compromised switch could jeopardize normal heart function in the neonate. Placental embolization in sheep is a reliable model of intrauterine growth restriction (IUGR).

Down-regulation of MEIS1 promotes the maturation of oxidative phosphorylation in perinatal cardiomyocytes.

Fetal cardiomyocytes shift from glycolysis to oxidative phosphorylation around the time of birth. Myeloid ecotropic viral integration site 1 (MEIS1) is a transcription factor that promotes glycolysis in hematopoietic stem cells. We reasoned that MEIS1 could have a similar role in the developing heart.