Fuelling Cerebral Activity in Exercising Man

Abstract

The metabolic response to brain activation in exercise might be expressed as the cerebral metabolic ratio (MR; uptake O 2 /glucose + 1/2 lactate). At rest, brain energy is provided by a balanced oxidation of glucose as MR is close to 6, but activation provokes a 'surplus' uptake of glucose relative to that of O 2 . Whereas MR remains stable during light exercise, it is reduced by 30% to 40% when exercise becomes demanding. The MR integrates metabolism in brain areas stimulated by sensory input from skeletal muscle, the mental effort to exercise and control of exercising limbs. The MR decreases during prolonged exhaustive exercise where blood lactate remains low, but when vigorous exercise raises blood lactate, the brain takes up lactate in an amount similar to that of glucose. This lactate taken up by the brain is oxidised as it does not accumulate within the brain and such pronounced brain uptake of substrate occurs independently of plasma hormones. The 'surplus' of glucose equivalents taken up by the activated brain may reach B10 mmol, that is, an amount compatible with the global glycogen level. It is suggested that a low MR predicts shortage of energy that ultimately limits motor activation and reflects a biologic background for 'central fatigue'.

Brain Lactate Metabolism: The Discoveries and the Controversies

“…Blood lactate is oxidized in the brain and more glucose is also consumed during exhaustive exercise, Brain lactate metabolism GA Dienel but there is also a decline in the oxygen/(glucose + 1 2 lactate) utilization ratio from B6 to as low as 1.7, and there is a large, unexplained excess carbohydrate taken up into brain that is not accounted for by oxidative metabolism or tissue metabolite accumulation or release (Dalsgaard, 2006;Quistorff et al, 2008;van Hall et al, 2009).…”

“…e Under 'resting' conditions, there is a slight efflux of lactate from the brain to blood as long as the blood lactate is relatively low (A, D; also see Madsen et al (1998); Linde et al (1999); Schmalbruch et al (2002)), in sharp contrast to the eye that releases large amounts of lactate under resting and activated conditions (C). When blood lactate increases above that in the brain during physical movement (D, rat) with moderate and strenuous exercise (E, human), lactate influx increases markedly and it becomes a significant brain fuel (Dalsgaard, 2006;Quistorff et al, 2008;van Hall et al, 2009). …”

Energy Metabolism in Astrocytes: High Rate of Oxidative Metabolism and Spatiotemporal Dependence on Glycolysis/Glycogenolysis

“…Lactate therefore enters the brain down its concentration gradient and is oxidized at a rate that equals glucose oxidation. Simultaneously, the metabolic ratio between ðCMR O 2 Þ and the glucose plus lactate metabolized falls as low as B3 (Dalsgaard, 2006). The cells that oxidize the lactate taken up into brain are not known, but this ratio reduction may occur for at least two reasons: (i) CSF, and presumably brain, levels of noradrenaline are greatly increased (Dalsgaard, 2006), suggesting a strong, widespread noradrenergic stimulation of glycogenolysis in astrocytes (Section Biogenic amines activate astrocytic metabolism).…”

“…Simultaneously, the metabolic ratio between ðCMR O 2 Þ and the glucose plus lactate metabolized falls as low as B3 (Dalsgaard, 2006). The cells that oxidize the lactate taken up into brain are not known, but this ratio reduction may occur for at least two reasons: (i) CSF, and presumably brain, levels of noradrenaline are greatly increased (Dalsgaard, 2006), suggesting a strong, widespread noradrenergic stimulation of glycogenolysis in astrocytes (Section Biogenic amines activate astrocytic metabolism). A large rise in glycogen utilization involving glucose degradation via glycogen ('shunting' of glucose via glycogen) would yield only 1 ATP per glucose, creating a deficit in glycolytically produced ATP and triggering a disproportionate increase in glycolysis compared with oxidative metabolism (Section Glycogen: an endogenous astrocytic source of glucose-6-phosphate); (ii) demand for glycolytically derived ATP or carbon (e.g., for filopodial transport processes or pyruvate carboxylation) would be expected to rise during activation, and contrary to glucose oxidation, no glycolytically derived energy is produced during lactate oxidation.…”

Brain Nonoxidative Carbohydrate Consumption is Not Explained by Export of an Unknown Carbon Source: Evaluation of the Arterial and Jugular Venous Metabolome

“…Cerebral activation, including changes in electrical (Kristeva-Feige et al, 2002;Rasmussen et al, 2004) and sensory (Friedman et al, 1991) activity during physical exercise, increases the brain's uptake of carbohydrate out of proportion to its oxygen uptake, that is cerebral activation is intimately coupled to so-called nonoxidative carbohydrate consumption (Dalsgaard, 2006;Fox et al, 1988;Ide et al, 1999).…”