Thyroid hormone increases fatty acid use in fetal ovine cardiac myocytes.

Cardiac metabolic substrate preference shifts at parturition from carbohydrates to fatty acids. We hypothesized that thyroid hormone (T ) and palmitic acid (PA) stimulate fetal cardiomyocyte oxidative metabolism capacity. T 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 T and PA, and oxygen consumption was measured with the Seahorse Bioanalyzer. Cardiomyocytes (130-day gestational age) exposed to elevated T in utero accumulated 42% more long-chain fatty acid droplets than did cells from vehicle-infused fetuses. In utero T increased myocardial mRNA levels of CD36, CPT1A, CPT1B, LCAD, VLCAD, HADH, IDH, PDK4, and caspase 9. In vitro exposure to T 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 T in cultured cardiomyocytes. T contributes to metabolic maturation of fetal cardiomyocytes. Prolonged exposure of fetal cardiomyocytes to PA, however, may impair oxidative capacity.