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 [18F]fluoro-deoxy-glucose ([18F]FDG). Fourteen healthy, right-handed men were studied after 35 min of bicycle exercise at exercise intensities corresponding to 30, 55 and 75% of on three separate days. [18F]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 micromol (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% of VO2max) 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.

Figure 1. Study design

The arrow indicates [¹⁸F]FDG injection 10 min after the beginning of exercise. Exercise duration was 35 min and the total study time was 120 min.

Figure 2. Time course of substrate availability and hormone output during exercise

Plasma glucose (A), serum insulin (B), plasma lactate (C), serum FFAs (D) and serum cortisol (E) concentrations from the start of the exercise to the end of the PET scan during three different exercise intensities. Values are expressed as mean ±s.d. Number of subjects is 14. *P < 0.01 and **P < 0.05 versus baseline; †P < 0.01 and ††P < 0.05 versus 30% intensity, and ‡P < 0.01 versus 55% intensity.

Figure 3. The effect of exercise intensity on brain glucose metabolism

The global and regional glucose uptake during exercise intensities of 30, 55 and 75% of V˙_O2max. *P < 0.002 versus 30% and #P < 0.002 versus 55% of V˙_O2max intensity. Global, whole brain; CRB, cerebellum; sFC, superior frontal cortex; mFC, medial frontal cortex; TC, temporal cortex; Tha, thalamus; dAC, dorsal part of the anterior cingulate.

Figure 4. The role of lactate during exercise

Association between global brain glucose uptake and serum lactate concentration at 30%, 55% and 75% of V˙_O2max, and during all exercise intensities.

Figure 5. The effect of exercise capacity

A, the result of voxel-based statistical analysis testing group-by-intensity level interaction. Statistical parametric map showing the region where decrease in glucose uptake between 30% and 75% of V˙_O2max exercise intensities was larger in subjects with higher exercise capacity (cluster-level P < 0.001 corrected for multiple comparisons). B, this same result visualized on the MRI template image. The colour intensity scale represents T-statistic values at voxel-level.