Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation
Candice N Baker1, Sarah A Gidus1, George F Price2
1Burnett School of Biomedical Sciences, University of Central Florida, College of Medicine, Orlando, Florida; and.
Insights
Adrenergic hormones are crucial for stimulating cardiac energy metabolism during embryonic development. Lacking these hormones significantly reduces ATP levels and impacts mitochondrial function in developing mouse embryos.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Mitochondrial Metabolism
Background:
- Cardiac energy demands rise significantly during embryonic to fetal development.
- Oxidative phosphorylation is vital for ATP production in mitochondria.
- Signaling mechanisms regulating the shift from anaerobic to aerobic metabolism are not well understood.
Purpose of the Study:
- To investigate the role of adrenergic hormones in stimulating cardiac energy metabolism during embryonic development.
- To test the hypothesis that adrenergic hormones are critical for this metabolic transition.
Main Methods:
- Examined ATP and ADP concentrations in mouse embryos with a targeted disruption of the dopamine β-hydroxylase (Dbh) gene, rendering them adrenergic-deficient.
- Measured cardiac extracellular acidification and oxygen consumption rates.
- Analyzed mitochondrial morphology and membrane potential.
- Administered adrenergic receptor agonists (isoproterenol, l-phenylephrine) to assess their effect on ATP levels.
Main Results:
- Adrenergic-deficient embryos exhibited a dramatic decrease in ATP and a significant drop in the ATP/ADP ratio (nearly 50-fold less than controls).
- Cardiac extracellular acidification and oxygen consumption rates were significantly reduced in Dbh-/- embryos.
- Mitochondria were larger and more branched in adrenergic-deficient hearts, though structurally intact.
- Maternal administration of adrenergic agonists ameliorated the reduced ATP levels in Dbh-/- embryos.
Conclusions:
- Adrenergic hormones are essential for stimulating cardiac energy metabolism during critical embryonic development.
- Adrenergic signaling via α- and β-adrenergic receptors modulates ATP concentrations in developing mouse embryos.
- Disruption of adrenergic signaling impairs cardiac energy metabolism and mitochondrial function during embryogenesis.
Abstract:
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 β-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 α- and β-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.
