Trajectories of brain lactate and re-visited oxygen-glucose index calculations do not support elevated non-oxidative metabolism of glucose across childhood
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Trajectories of brain lactate and re-visited oxygen-glucose index calculations do not support elevated non-oxidative metabolism of glucose across childhood. / Benveniste, Helene; Dienel, Gerald; Jacob, Zvi; Lee, Hedok; Makaryus, Rany; Gjedde, Albert; Hyder, Fahmeed; Rothman, Douglas L.
In: Frontiers in Neuroscience, Vol. 12, 631, 2018.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Trajectories of brain lactate and re-visited oxygen-glucose index calculations do not support elevated non-oxidative metabolism of glucose across childhood
AU - Benveniste, Helene
AU - Dienel, Gerald
AU - Jacob, Zvi
AU - Lee, Hedok
AU - Makaryus, Rany
AU - Gjedde, Albert
AU - Hyder, Fahmeed
AU - Rothman, Douglas L.
N1 - Publisher Copyright: © 2018 Benveniste, Dienel, Jacob, Lee, Makaryus, Gjedde, Hyder and Rothman.
PY - 2018
Y1 - 2018
N2 - Brain growth across childhood is a dynamic process associated with specific energy requirements. A disproportionately higher rate of glucose utilization (CMRglucose) compared with oxygen consumption (CMRO2) was documented in children's brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the CMRglucose-CMRO2 mismatch, and lactate production is considered a major contender. The ~33% excess CMRglucose equals 0.18 μmol glucose/g/min and predicts lactate release of 0.36 μmol/g/min. To validate such scenario, we measured the brain lactate concentration ([Lac]) in 65 children to determine if indeed lactate accumulates and is high enough to (1) account for the glucose consumed in excess of oxygen and (2) support a high rate of lactate efflux from the young brain. Across childhood, brain [Lac] was lower than predicted, and below the range for adult brain. In addition, we re-calculated the CMRglucose-CMRO2 mismatch itself by using updated lumped constant values. The calculated cerebral metabolic rate of lactate indicated a net influx of 0.04 μmol/g/min, or in terms of CMRglucose, of 0.02 μmol glucose/g/min. Accumulation of [Lac] and calculated efflux of lactate from brain are not consistent with the increase in non-oxidative metabolism of glucose. In addition, the value for the lumped constant for [18F]fluorodeoxyglucose has a high impact on calculated CMRglucose and use of updated values alters or eliminates the CMRglucose-CMRO2 mismatch in developing brain. We conclude that the presently-accepted notion of non-oxidative metabolism of glucose during childhood must be revisited and deserves further investigations.
AB - Brain growth across childhood is a dynamic process associated with specific energy requirements. A disproportionately higher rate of glucose utilization (CMRglucose) compared with oxygen consumption (CMRO2) was documented in children's brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the CMRglucose-CMRO2 mismatch, and lactate production is considered a major contender. The ~33% excess CMRglucose equals 0.18 μmol glucose/g/min and predicts lactate release of 0.36 μmol/g/min. To validate such scenario, we measured the brain lactate concentration ([Lac]) in 65 children to determine if indeed lactate accumulates and is high enough to (1) account for the glucose consumed in excess of oxygen and (2) support a high rate of lactate efflux from the young brain. Across childhood, brain [Lac] was lower than predicted, and below the range for adult brain. In addition, we re-calculated the CMRglucose-CMRO2 mismatch itself by using updated lumped constant values. The calculated cerebral metabolic rate of lactate indicated a net influx of 0.04 μmol/g/min, or in terms of CMRglucose, of 0.02 μmol glucose/g/min. Accumulation of [Lac] and calculated efflux of lactate from brain are not consistent with the increase in non-oxidative metabolism of glucose. In addition, the value for the lumped constant for [18F]fluorodeoxyglucose has a high impact on calculated CMRglucose and use of updated values alters or eliminates the CMRglucose-CMRO2 mismatch in developing brain. We conclude that the presently-accepted notion of non-oxidative metabolism of glucose during childhood must be revisited and deserves further investigations.
KW - Aerobic glycolysis
KW - Bioenergetics
KW - Brain
KW - Child
KW - Development
KW - Lactate
KW - Non-oxidative metabolism
U2 - 10.3389/fnins.2018.00631
DO - 10.3389/fnins.2018.00631
M3 - Journal article
AN - SCOPUS:85053113392
VL - 12
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
SN - 1662-4548
M1 - 631
ER -
ID: 286485790