High intensity exercise decreases global brain glucose uptake in humans

Abstract

Physiological activation increases glucose uptake locally in the brain. However, it is not known how high intensity exercise affects regional and global brain glucose uptake. The effect of exercise intensity and exercise capacity on brain glucose uptake was directly measured using positron emission tomography (PET) and 18 F]FDG was injected 10 min after the start of the exercise. Thereafter exercise was continued for another 25 min. PET scanning of the brain was conducted after completion of the exercise. Regional glucose metabolic rate (rGMR) decreased in all measured cortical regions as exercise intensity increased. The mean decrease between the highest and lowest exercise intensity was 32% globally in the brain (38.6 ± 4.6 versus 26.1 ± 5.0 µmol (100 g) −1 min −1 , P < 0.001). Lactate availability during exercise tended to correlate negatively with the observed brain glucose uptake. In addition, the decrease in glucose uptake in the dorsal part of the anterior cingulate cortex (37% versus 20%, P < 0.05 between 30% and 75% ofV O 2 max ) was significantly more pronounced in subjects with higher exercise capacity. These results demonstrate that brain glucose uptake decreases with increase in exercise intensity. Therefore substrates other than glucose, most likely lactate, are utilized by the brain in order to compensate the increased energy needed to maintain neuronal activity during high intensity exercise. Moreover, it seems that exercise training could be related to adaptive metabolic changes locally in the frontal cortical regions.

Fuelling Cerebral Activity in Exercising Man

“…Running and cycling elicit widespread increases in local CMR glucose compared with the rest, as determined by PET (Kemppainen et al, 2005;Tashiro et al, 2001), but at higher cycling intensities CMR glucose decreases with the increasing arterial lactate, possibly because of substitution for glucose (Kemppainen et al, 2005).…”

“…As for lactate serving as a precursor for biosynthesis, gluconeogenesis in astrocytes and neurons is negligible (Swanson et al, 1990) and glycogen synthesis from lactate does not appear to be significant (Brown et al, 2003;Ide et al, 1969). In regard to metabolism, infusion of lactate spares glucose in resting subjects (Smith et al, 2003), and after exercise (Kemppainen et al, 2005) and on the cellular level lactate is metabolised by both neurons (Schurr et al, 1997) and astrocytes (Dringen et al, 1995). Conversion of lactate to pyruvate and subsequent oxidation yields energy metabolites that may inhibit glycolysis (Ide et al, 1969;Tabernero et al, 1996), which could explain the glucosesparing effect of lactate (Bouzier-Sore et al, 2003;Kemppainen et al, 2005;Smith et al, 2003).…”

“…Furthermore, at different exercise intensities, cortical lactate metabolism seems elevated in well-trained compared with untrained subjects (Kemppainen et al, 2005) and that could be of importance for exercise capacity. During exercise, the lactate taken up by the brain is not released to blood within a 1-h recovery period (Dalsgaard et al, 2002;Ide et al, 2000b) and it does not accumulate in CSF or within the brain as determined by MRS (Figure 4) (Dalsgaard et al, 2004b).…”

“…During whole-body exercise, measurement of regional cerebral blood flow (rCBF) and metabolism is hindered by body movement and is feasible only as post-versus pre-exercise comparison, for example, with position emission tomography (PET) (Kemppainen et al, 2005;Tashiro et al, 2001) and singlephoton emission computer tomography (SPECT) (Williamson et al, 1996). Alternatively, an increase in blood flow of B25% is observed on the 'arterial side' of the activated brain region, as visualized with Doppler ultrasound in the internal carotid artery (Hellstrom et al, 1996) and as noted for the mean blood flow velocity (V mean ) in major cerebral arteries (Figure 1) (Ide and Secher, 2000;Jorgensen, 1995).…”

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

“…Thus, lactate to some extent replaces glucose as substrate (Kemppainen et al, 2005;van Hall et al, 2009), albeit it is accepted that brain activation increases glucose uptake (Fox et al, 1988;Madsen et al, 1999). The fate of the lactate is, therefore, of special interest.…”