Abstract Cardiac metabolic substrate preference shifts at parturition from carbohydrates to fatty acids. We hypothesized that thyroid hormone (T3) and palmitic acid (PA) stimulate fetal cardiomyocyte oxidative metabolism capacity. T3 was infused into fetal sheep to a target of 1.5 nM. Dispersed cardiomyocytes were assessed for lipid uptake and droplet formation with BODIPY‐labeled fatty acids. Myocardial expression levels were assessed PCR. Cardiomyocytes from naïve fetuses were exposed to T3 and PA, and oxygen consumption was measured with the Seahorse Bioanalyzer. Cardiomyocytes (130‐day gestational age) exposed to elevated T3 in utero accumulated 42% more long‐chain fatty acid droplets than did cells from vehicle‐infused fetuses. In utero T3 increased myocardial mRNA levels of CD36, CPT1A, CPT1B, LCAD, VLCAD, HADH, IDH, PDK4, and caspase 9. In vitro exposure to T3 increased maximal oxygen consumption rate in cultured cardiomyocytes in the absence of fatty acids, and when PA was provided as an acute (30 min) supply of cellular energy. Longer‐term exposure (24 and 48 h) to PA abrogated increased oxygen consumption rates stimulated by elevated levels of T3 in cultured cardiomyocytes. T3 contributes to metabolic maturation of fetal cardiomyocytes. Prolonged exposure of fetal cardiomyocytes to PA, however, may impair oxidative capacity.
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