Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics

eLife

Simon C Johnson¹  Rebecca Bornstein²  Amanda Pan³  Margaret M Sedensky³  Kyung Yeon Park³  Grace X Sun³  Brittany M Johnson³  Arielle Freed³  Julia Stokes³  Philip G Morgan³  Hailey Worstman³  Sangwook Jung³  John Snell⁴  Kevin N Su⁵ 

[1] Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United States;University of Washington School of Dentistry, Seattle, United States;Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, United States;Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United States;Department of Pathology, University of Washington, Seattle, United States;

关键词: anesthesia;    fatty acid oxidation;    mitochondria;    neonate;    metabolism;    ketogenesis;   

DOI  :  10.7554/eLife.65400

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown