Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics

Stokes, Julia, Freed, Arielle, Bornstein, Rebecca, Su, Kevin N, Snell, John, Pan, Amanda, Sun, Grace X, Park, Kyung Yeon, Jung, Sangwook, Worstman, Hailey, Johnson, Brittany M, Morgan, Philip G, Sedensky, Margaret M and Johnson, Simon (2021) Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics. eLife, 10. ISSN 2050-084X

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Volatile anesthetics (VAs) are widely used in medicine, but the mechanisms underlying their effects remain ill-defined. Though routine anesthesia is safe in healthy individuals, instances of sensitivity are well documented, and there has been significant concern regarding the impact of VAs on neonatal brain development. Evidence indicates that VAs have multiple targets, with anesthetic and non-anesthetic effects mediated by neuroreceptors, ion channels, and the mitochondrial electron transport chain. Here, we characterize an unexpected metabolic effect of VAs in neonatal mice. Neonatal blood β-hydroxybutarate (β-HB) is rapidly depleted by VAs at concentrations well below those necessary for anesthesia. β-HB in adults, including animals in dietary ketosis, is unaffected. Depletion of β-HB is mediated by citrate accumulation, malonyl-CoA production by acetyl-CoA carboxylase, and inhibition of fatty acid oxidation. Adults show similar significant changes to citrate and malonyl-CoA, but are insensitive to malonyl-CoA, displaying reduced metabolic flexibility compared to younger animals.

Item Type: Article
Additional Information: Funding information: NIH Office of the Director R01GM133865; NIH Office of the Director R01GM118514; NIH Office of the Director R00GM126147
Uncontrolled Keywords: 3-Hydroxybutyric Acid, Acetyl-CoA Carboxylase/metabolism, Anesthetics/metabolism, Animals, Citrates/metabolism, Citric Acid/metabolism, Fatty Acids/metabolism, Female, Glucose/metabolism, Hypoglycemia, Isoflurane/metabolism, Ketosis, Male, Malonyl Coenzyme A/metabolism, Mice, Mice, Inbred C57BL, Mitochondria, Oxidation-Reduction
Subjects: C500 Microbiology
C600 Sports Science
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Rachel Branson
Date Deposited: 06 Dec 2022 16:33
Last Modified: 06 Dec 2022 16:45

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