Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain

TY - JOUR

T1 - Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain

AU - Overgaard, Morten

AU - Rasmussen, Peter

AU - Bohm, Aske M

AU - Seifert, Thomas

AU - Brassard, Patrice

AU - Zaar, Morten

AU - Homann, Pernille Halberg

AU - Evans, Kevin A

AU - Nielsen, Henning B

AU - Secher, Niels H

AU - Nielsen, Henning M Bay

PY - 2012/7

Y1 - 2012/7

N2 - Lactate is shuttled between organs, as demonstrated in the Cori cycle. Although the brain releases lactate at rest, during physical exercise there is a cerebral uptake of lactate. Here, we evaluated the cerebral lactate uptake and release in hypoxia, during exercise and when the two interventions were combined. We measured cerebral lactate turnover via a tracer dilution method ([1-13C]lactate), using arterial to right internal jugular venous differences in 9 healthy individuals (5 males and 4 females), at rest and during 30 min of submaximal exercise in normoxia and hypoxia (FiO 2 10%, arterial oxygen saturation 72±10%, mean±SD). Whole-body lactate turnover increased 3.5- fold and 9-fold at two workloads in normoxia and 18-fold during exercise in hypoxia. Although middle cerebral artery mean flow velocity increased during exercise in hypoxia, calculated cerebral mitochondrial oxygen tension decreased by 13 mmHg (P<0.001). At the same time, cerebral lactate release increased from 0.15 ± 0.1 to 0.8 ± 0.6 mmol min-1 (P<0.05), corresponding to ~10% of cerebral energy consumption. Concurrently, cerebral lactate uptake was 1.0 ± 0.9 mmol min-1 (P<0.05), of which 57 ± 9% was oxidized, demonstrating that lactate oxidation may account for up to ~33% of the energy substrate used by the brain. These results support the existence of a cell-cell lactate shuttle that may involve neurons and astrocytes.

AB - Lactate is shuttled between organs, as demonstrated in the Cori cycle. Although the brain releases lactate at rest, during physical exercise there is a cerebral uptake of lactate. Here, we evaluated the cerebral lactate uptake and release in hypoxia, during exercise and when the two interventions were combined. We measured cerebral lactate turnover via a tracer dilution method ([1-13C]lactate), using arterial to right internal jugular venous differences in 9 healthy individuals (5 males and 4 females), at rest and during 30 min of submaximal exercise in normoxia and hypoxia (FiO 2 10%, arterial oxygen saturation 72±10%, mean±SD). Whole-body lactate turnover increased 3.5- fold and 9-fold at two workloads in normoxia and 18-fold during exercise in hypoxia. Although middle cerebral artery mean flow velocity increased during exercise in hypoxia, calculated cerebral mitochondrial oxygen tension decreased by 13 mmHg (P<0.001). At the same time, cerebral lactate release increased from 0.15 ± 0.1 to 0.8 ± 0.6 mmol min-1 (P<0.05), corresponding to ~10% of cerebral energy consumption. Concurrently, cerebral lactate uptake was 1.0 ± 0.9 mmol min-1 (P<0.05), of which 57 ± 9% was oxidized, demonstrating that lactate oxidation may account for up to ~33% of the energy substrate used by the brain. These results support the existence of a cell-cell lactate shuttle that may involve neurons and astrocytes.

U2 - 10.1096/fj.11-191999

DO - 10.1096/fj.11-191999

M3 - Journal article

C2 - 22441982

SN - 0892-6638

SP - 3012

EP - 3020

JO - F A S E B Journal

JF - F A S E B Journal

ER -