Toshihiko Fujimoto

High intensity exercise decreases global brain glucose uptake in humans

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 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% of ) 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.

Skeletal muscle glucose uptake response to exercise in trained and untrained men.

PURPOSE Endurance training enhances skeletal muscle glucose uptake at rest, but the responses to different exercise intensities are unknown. In the present study, we tested whether glucose uptake is enhanced in trained men during low-, moderate-, and high-intensity exercise as compared with untrained men. METHODS Seven trained and untrained men were studied without any dietary manipulation during bicycle exercise at relative intensities of 30%, 55%, and 75% of maximal oxygen consumption ([OV0312]O(2max)) on three separate days. Glucose uptake in the quadriceps femoris muscle was directly measured using positron emission tomography (PET) and 18F-fluoro-deoxy-glucose ([18F]FDG). [18F]FDG was injected 10 min after the start of the exercise. Thereafter exercise was continued for another 25 min. PET scanning was conducted immediately after completion of the exercise. The measured glucose uptake values reflect the situation during exercise due to chemical characteristics of the [18F]FDG. RESULTS Muscle glucose uptake increased from 30% to 55% [OV0312]O(2max) intensity exercise similarly in both groups (P < 0.05). However, from 55% to 75% [OV0312]O(2max) intensity exercise, only athletes were able to further enhance glucose uptake. Furthermore, at highest intensity, glucose uptake was significantly higher in trained than in untrained men (236.6 +/- 29.6 vs 176.3 +/- 22.4 micromol.kg-1.min-1, P < 0.05). There were no differences in plasma glucose, insulin, or lactate in any time point at 75% [OV0312]O(2max) intensity between groups. CONCLUSIONS These results show that skeletal muscle glucose uptake is higher in trained than in untrained men at high relative exercise intensity, although at lower relative exercise intensities no differences are observed. Thus, endurance training improves the capacity of contraction-induced glucose uptake in skeletal muscle.

Whole-body metabolic map with positron emission tomography of a man after running

body tomograph SET2400W (Shimadzu Co, Japan), with an intrinsic spatial resolution of 3·9 mm. The figure shows PET images of the subject lying supine. Correction of tissue attenuation was made after emission acquisition (postinjection transmission) using a needle Ge/Ga source. We found that F-FDG uptake was increased in the soleus and gastrocemius muscles—those most exercised in endurance running. Lesser accumulations of F-FDG in other muscles including those of the thighs were also noted. These images indicate that PET can identify muscles used in physical activity. The amount of radioactivity required for imaging can probably be reduced to less than 40 MBq, corresponding to a whole body radiation dose of around 0·5 mSv, equivalent to half the exposure of an abdominal radiograph. PET mapping of muscle activity may provide useful information for sports and rehabilitation medicine.

Application of positron emission tomography to neuroimaging in sports sciences.

To investigate exercise-induced regional metabolic and perfusion changes in the human brain, various methods are available, such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI), near-infrared spectroscopy (NIRS) and electroencephalography (EEG). In this paper, details of methods of metabolic measurement using PET, [(18)F]fluorodeoxyglucose ([(18)F]FDG) and [(15)O]radio-labelled water ([(15)O]H(2)O) will be explained. Functional neuroimaging in the field of neuroscience was started in the 1970s using an autoradiography technique on experimental animals. The first human functional neuroimaging exercise study was conducted in 1987 using a rough measurement system known as (133)Xe inhalation. Although the data was useful, more detailed and exact functional neuroimaging, especially with respect to spatial resolution, was achieved by positron emission tomography. Early studies measured the cerebral blood flow changes during exercise. Recently, PET was made more applicable to exercise physiology and psychology by the use of the tracer [(18)F]FDG. This technique allowed subjects to be scanned after an exercise task is completed but still obtain data from the exercise itself, which is similar to autoradiography studies. In this report, methodological information is provided with respect to the recommended protocol design, the selection of the scanning mode, how to evaluate the cerebral glucose metabolism and how to interpret the regional brain activity using voxel-by-voxel analysis and regions of interest techniques (ROI). Considering the important role of exercise in health promotion, further efforts in this line of research should be encouraged in order to better understand health behavior. Although the number of research papers is still limited, recent work has indicated that the [(18)F]FDG-PET technique is a useful tool to understand brain activity during exercise.

Increasing exercise intensity reduces heterogeneity of glucose uptake in human skeletal muscles.

Proper muscle activation is a key feature of survival in different tasks in daily life as well as sports performance, but can be impaired in elderly and in diseases. Therefore it is also clinically important to better understand the phenomenon that can be elucidated in humans non-invasively by positron emission tomography (PET) with measurements of spatial heterogeneity of glucose uptake within and among muscles during exercise. We studied six healthy young men during 35 minutes of cycling at relative intensities of 30% (low), 55% (moderate), and 75% (high) of maximal oxygen consumption on three separate days. Glucose uptake in the quadriceps femoris muscle group (QF), the main force producing muscle group in recreational cycling, and its four individual muscles, was directly measured using PET and 18F-fluoro-deoxy-glucose. Within-muscle heterogeneity was determined by calculating the coefficient of variance (CV) of glucose uptake in PET image voxels within the muscle of interest, and among-muscles heterogeneity of glucose uptake in QF was expressed as CV of the mean glucose uptake values of its separate muscles. With increasing intensity, within-muscle heterogeneity decreased in the entire QF as well as within its all four individual parts. Among-muscles glucose uptake heterogeneity also decreased with increasing intensity. However, mean glucose uptake was consistently lower and heterogeneity higher in rectus femoris muscle that is known to consist of the highest percentage of fast twitch type II fibers, compared to the other three QF muscles. In conclusion, these results show that in addition to increased contribution of distinct muscle parts, with increases in exercise intensity there is also an enhanced recruitment of muscle fibers within all of the four heads of QF, despite established differences in muscle-part specific fiber type distributions. Glucose uptake heterogeneity may serve as a useful non-invasive tool to elucidate muscle activation in aging and diseased populations.

Evaluation of individual skeletal muscle activity by glucose uptake during pedaling exercise at different workloads using positron emission tomography

Skeletal muscle glucose uptake closely reflects muscle activity at exercise intensity levels <55% of maximal oxygen consumption (VO2max). Our purpose was to evaluate individual skeletal muscle activity from glucose uptake in humans during pedaling exercise at different workloads by using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET). Twenty healthy male subjects were divided into two groups (7 exercise subjects and 13 control subjects). Exercise subjects were studied during 35 min of pedaling exercise at 40 and 55% VO2max exercise intensities. FDG was injected 10 min after the start of exercise or after 20 min of rest. PET scanning of the whole body was conducted after completion of the exercise or rest period. In exercise subjects, mean FDG uptake [standardized uptake ratio (SUR)] of the iliacus muscle and muscles of the anterior part of the thigh was significantly greater than uptake in muscles of control subjects. At 55% VO2max exercise, SURs of the iliacus muscle and thigh muscles, except for the rectus femoris, increased significantly compared with SURs at 40% VO2max exercise. Our results are the first to clarify that the iliacus muscle, as well as the muscles of the anterior thigh, is the prime muscle used during pedaling exercise. In addition, the iliacus muscle and all muscles in the thigh, except for the rectus femoris, contribute when the workload of the pedaling exercise increases from 40 to 55% VO2max.

Whole-body energy mapping under physical exercise using positron emission tomography.

We attempted to visualize dynamic adjustment of glucose utilization in humans in the whole-body organs during physical exercise by using three-dimensional positron emission tomography (3D-PET) and [18F]-2-fluoro-deoxy-glucose (FDG). Twelve healthy male volunteers collaborated on the study; six subjects were assigned to the resting control group (C) and the other six to the running group (E). Group E subjects performed running on a flat road for 35 min. After 15 min of running, subjects injected FDG and kept on running thereafter for another 20 min. Group C subjects sat on a comfortable chair in a quiet room for 35 min after the injection of FDG. After scanning by PET, the regions of interest (ROIs) were manually set on brain, heart, thorax, abdomen, lower extremities, and the rest of the body on the corresponding transaxial images. The uptake of FDG in each region was evaluated as the % fraction of FDG accumulation relative to the total amount of whole-body accumulation. The results revealed increase of FDG uptake after running in the lower leg muscles from 24.6 +/- 9.5% to 43.1 +/- 4.7% and in the heart from 2.3 +/- 0.4% to 2.8 +/- 0.6%. The differences were significant (P < 0.05). These increases reflect the rise in energy consumption in leg and heart muscles and were balanced by the reduction of energy consumption in the other part of the body. FDG uptake in the abdominal region reduced from 37.3 +/- 7.2% to 19.7 +/- 4.9%. However, FDG uptake in the brain remained stable, i.e., 11.9 +/- 2.8% at rest and 10.3 +/- 2.5% after exercise. Thus, 3D-PET is a tool to visualize the dynamic adjustment of energy consumption during physical exercise in humans.

Redistribution of whole-body energy metabolism by exercise: a positron emission tomography study

AbstractObjectiveOur aim was to evaluate changes in glucose metabolism of skeletal muscles and viscera induced by different workloads using 18F-2-fluoro-2-deoxyglucose ([18F]FDG) and three-dimensional positron emission tomography (3-D PET).MethodsFive male volunteers performed ergometer bicycle exercise for 40 min at 40% and 70% of the maximal O2 consumption (

Molecular and Functional Imaging for Drug Development and Elucidation of Disease Mechanisms Using Positron Emission Tomography (PET)

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