Cerebral glucose and lactate consumption during cerebral activation by physical activity in humans

Abstract

At rest, the brain takes up oxygen and carbohydrate at an ~6:1 ratio. Exercise increases systemic lactate availability reducing this to as little as 1.7:1 despite a ~20% increase in cerebral metabolic rate for oxygen (CMRo₂), thus indicating a disproportionate increase of carbohydrate metabolism. Underlining mechanisms and metabolic fate for the augmented lactate uptake are unknown. This meta-analysis examines whether adrenergic activation explains the increased lactate uptake, cerebral lactate release following cerebral activation compensates for the extra carbohydrate uptake during exercise, and cerebral lactate uptake spares glucose as fuel. Ten studies (n=96) measuring arteriovenous differences for lactate, glucose, and oxygen and cerebral blood flow were included. Cerebral lactate uptake increased during brain activation by whole-body exercise compared to the resting state. Unlike glucose, lactate uptake is proportional to its arterial concentration but is unaffected by sympathetic activity. Following exercise, significant cerebral lactate released as arterial lactate levels decreased, which may balance the surplus lactate uptake in the brain during physical activity in the long term. Finally, cerebral glucose uptake was reduced by ~25% in relation to CMRo₂ when cerebral lactate uptake increased, suggesting, in part, preferential lactate consumption during activation. This meta-analysis favors the notion that cerebral lactate uptake is mainly passively governed by its availability, but when lactate is available, lactate supplements glucose and supports an increase in cerebral energy metabolism in an activity-dependent manner.

Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia

“…Basal lactate uptake into the brain in our study at euglycemia (V in , 0.14 μmol/min/g at plasma level 2-3 mM) is consistent with several other studies that have measured this parameter in the context of rest and exercise in healthy subjects, as summarized by Rasmussen et al (35). In this study, we found that one of the adaptations to recurrent hypoglycemia was a significant enhancement of lactate uptake (V in , 0.26 μmol/g/min) into the brain under hypoglycemia ( Figure 4A).…”

The metabolic trinity, glucose–glycogen–lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression

“…Locus coeruleus stimulation increases brain vascular water permeability and an ␣-adrenergic blocker reduces water permeability [56], whereas increased water permeability during seizures was unaffected by unilateral locus coeruleus lesion [25]. However, water derived from blood is considered insufficient to support perivascular metabolite clearance because hemoglobin levels across brain do not change during exercise [57]. Given the large flow differences for blood and perivascular-lymphatic flow (in rats: ∼1 mL/min/g blood flow vs. ∼0.3 L/g/min perivascular flow [5]; Note: the latter rate approximates calculated production of metabolic water from glucose oxidation, without including CSF clearance), even a small diversion of water from blood could have a high impact on lymphatic drainage.…”

The Astrocyte: Powerhouse and Recycling Center

“…This fuel monodependence has been explained by the inability of albumin-bound fatty acids to cross the blood -brain barrier and the fact that ATP production requires less oxygen from glucose than from fat. Minor substrates, like lactate and ketone bodies, may become significant if their blood levels are elevated, as occurs in strenuous exercise or when fasting (Dalsgaard et al 2004;Yellen 2008;Rasmussen et al 2011). Glucose enters the brain via the endothelial transporter GLUT1 and is then captured by astrocytic endfeet, which are also rich in GLUT1 (Kacem et al 1998).…”