TY - JOUR TI - Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics AU - Stokes, Julia AU - Freed, Arielle AU - Bornstein, Rebecca AU - Su, Kevin N AU - Snell, John AU - Pan, Amanda AU - Sun, Grace X AU - Park, Kyung Yeon AU - Jung, Sangwook AU - Worstman, Hailey AU - Johnson, Brittany M AU - Morgan, Philip G AU - Sedensky, Margaret M AU - Johnson, Simon C A2 - Isales, Carlos A2 - Zaidi, Mone VL - 10 PY - 2021 DA - 2021/07/13 SP - e65400 C1 - eLife 2021;10:e65400 DO - 10.7554/eLife.65400 UR - https://doi.org/10.7554/eLife.65400 AB - 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. KW - anesthesia KW - fatty acid oxidation KW - mitochondria KW - neonate KW - metabolism KW - ketogenesis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -