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Lactate fuels the human brain during exercise

Bjørn Quistorff^*, Niels H. Secher^, and Johannes J. Van Lieshout^,||,1

^* Department of Biomedical Sciences,

Department of Anesthesiology, and

The Copenhagen Muscle Research Center, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; and

Department of Internal Medicine, Medium Care Unit, and

^|| Laboratory for Clinical Cardiovascular Physiology, Center for Heart Failure Research, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

¹Correspondence: Department of Internal Medicine, Medium Care Unit, Room F7-205, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: j.j.vanlieshout{at}amc.uva.nl

The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up lactate in proportion to the arterial concentration. Cerebral lactate uptake, together with glucose uptake, is larger than the uptake accounted for by the concomitant O₂ uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O₂/(glucose+ lactate)] from a resting value of 6 to <2. The CMR also decreases when plasma lactate is not increased, as during prolonged exercise, cerebral activation associated with mental activity, or exposure to a stressful situation. The CMR decrease is prevented with combined β₁- and β₂-adrenergic receptor blockade but not with β₁-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a β₂-adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood-brain barrier. The pattern of CMR decrease under various forms of brain activation suggests that lactate may partially replace glucose as a substrate for oxidation. Thus, the notion of the human brain as an obligatory glucose consumer is not without exceptions.—Quistorff, B., Secher, N. H., and Van Lieshout, J. J. Lactate fuels the human brain during exercise.

Key Words: energy metabolism • glucose • oxygen

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