Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation
Abbreviated Journal Title
Am. J. Physiol.-Endocrinol. Metab.
heart failure; adrenergic hormones; mitochondria; metabolism; glycolysis; PHENYLETHANOLAMINE N-METHYLTRANSFERASE; IN-VITRO; FATTY-ACID; RAT-HEART; OXIDATIVE-PHOSPHORYLATION; MITOCHONDRIAL MORPHOLOGY; LIVER; PHOSPHORYLASE; MTDNA MAINTENANCE; FETAL-DEVELOPMENT; FAILING HEART; Endocrinology & Metabolism; Physiology
As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine beta-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or L-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh(-/-) embryos, suggesting that alpha- and beta-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development.
American Journal of Physiology-Endocrinology and Metabolism
"Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation" (2015). Faculty Bibliography 2010s. 6410.