Tyrosine as a Mechanistic-Based Biomarker for Brain Glycogen Decrease and Supercompensation With Endurance Exercise in Rats: A Metabolomics Study of Plasma

Brain glycogen localized in astrocytes produces lactate as an energy source and/or a signal factor to serve neuronal functions involved in memory formation and exercise endurance. In rodents, four weeks of chronic moderate exercise enhancing endurance and cognition increases brain glycogen in the hippocampus and cortex, which is an adaption of brain metabolism achieved through exercise. Although this brain adaptation is likely induced due to the accumulation of acute endurance exercise¬–induced brain glycogen supercompensation, its molecular mechanisms and biomarkers are unidentified. Since noradrenaline synthesized from blood-borne tyrosine activates not only glycogenolysis but also glycogen synthesis in astrocytes, we hypothesized that blood tyrosine is a mechanistic-based biomarker of the acute exercise–induced brain glycogen supercompensation. To test this hypothesis, we used a rat model of endurance exercise, a microwave irradiation for accurate detection of glycogen in the brain (the cortex, hippocampus, and hypothalamus), and capillary electrophoresis mass spectrometry–based metabolomics to observe the comprehensive metabolic profile of the blood. Endurance exercise induced fatigue factors such as a decrease in blood glucose, an increase in blood lactate, and a depletion of muscle glycogen, but those parameters recovered to basal levels 6 h after exercise. Brain glycogen decreased during endurance exercise and showed the supercompensation 6 h after exercise. Metabolomics detected 186 metabolites in plasma, and 110 metabolites changed significantly during and following exhaustive exercise. Brain glycogen levels correlated negatively with plasma glycogenic amino acids (serine, proline, threonine, glutamate, methionine, tyrosine, and tryptophan) (r < −0.9). This is the first study producing a broad picture of plasma metabolite changes due to endurance exercise–induced brain glycogen supercompensation. Our findings suggest that plasma glycogenic amino acids are sensitive indicators of brain glycogen levels with endurance exercise. In particular, plasma tyrosine as a precursor of brain noradrenaline might be a valuable mechanistic-based biomarker for predicting brain glycogen dynamics with endurance exercise.