title: Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain.
abstract: 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-(13)C]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 (F(i)o(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.
authors.affiliation: Department of Anesthesia, The Copenhagen Muscle Research Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Overgaard
authors.forename: Peter
authors.initials: P
authors.lastname: Rasmussen
authors.forename: Aske M
authors.initials: AM
authors.lastname: Bohm
authors.forename: Thomas
authors.initials: T
authors.lastname: Seifert
authors.forename: Patrice
authors.initials: P
authors.lastname: Brassard
authors.forename: Morten
authors.initials: M
authors.lastname: Zaar
authors.forename: Pernille
authors.initials: P
authors.lastname: Homann
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Evans
authors.forename: Henning B
authors.initials: HB
authors.lastname: Nielsen
authors.forename: Niels H
authors.initials: NH
authors.lastname: Secher
mesh_terms: D000328:Adult; D001693:Biological Transport, Active; D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D055815:Young Adult
chemical_list: D019344:Lactic Acid