Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans

Abstract

Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that exercise protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the kynurenine metabolism away from the neurotoxic kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present study, we investigated the effect of exercise on kynurenine metabolism in humans. KAT gene and protein expression was increased in the muscles of endurance-trained subjects compared with untrained subjects. Endurance exercise caused an increase in plasma KYNA within the first hour after exercise. In contrast, a bout of high-intensity eccentric exercise did not lead to increased plasma KYNA concentration. Our results show that regular endurance exercise causes adaptations in kynurenine metabolism which can have implications for exercise recommendations for patients with depressive disorder.

Twelve-week physical exercise does not have a long-lasting effect on kynurenines in plasma of depressed patients

“…These results are in accordance with the results in healthy individuals reported by Schlittler et al, which showed that KYNA levels increased 1 h after intense exercise, but returned to baseline levels as quickly as 5 h later 11. This showed a pattern similar to PGC-1α that increased rapidly after exercise, but returned to baseline within 6–24 h 22.…”

“…Another study found no difference in plasma kynurenine levels in patients with major depression (n=38) or healthy controls (n=48) after 1 week of daily moderate physical activity, although depressive symptoms in patients improved during the intervention 10. Schlittler et al explored the effects of intense physical activity on KYNA levels and muscular PGC-1α1 in healthy subjects 11. The authors showed that endurance exercise of 150 km road cycling increased the expression of PGC-1α1 and kynurenine aminotransferases in muscles and led to an increase of KYNA in peripheral blood which was observed 1 h after the exercise.…”

Probiotic Supplements Beneficially Affect Tryptophan–Kynurenine Metabolism and Reduce the Incidence of Upper Respiratory Tract Infections in Trained Athletes: A Randomized, Double-Blinded, Placebo-Controlled Trial

“…Interestingly, VO 2max correlated with pre-exercise Trp levels supporting a role of Trp metabolism in training performance. It could further relate to the recent findings of Kyn metabolism in skeletal muscle mediating resilience to stress-induced depression with endurance training, whereas less energetically demanding exercise protocols, such as high-force eccentric exercise, did not lead to adaptations in Kyn metabolism [41,43]. …”

“…However, it was not determined whether higher Kyn/Trp ratios were observed, particularly in those individuals who experienced an infection close to the end of the study and it still remains to be elucidated whether there is a more direct association between probiotic supplementation and reduced Trp breakdown. Alternatively, different training loads between groups may have affected Trp metabolism, rather than the actions of the probiotic, since regular endurance exercise causes adaptations in Kyn metabolism [41]. …”

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

“…KAT (I, II, and III) protein levels in mouse gastrocnemius muscle can be induced by exercise, but not chronic mild stress [22]. Importantly, exercise training increase KATs (I, II, III, and IV) mRNA and protein levels in human vastus lateralis skeletal muscle [22, 185]. KATs are insensitive to minerals changes, but sensitive to dietary vitamin B6, which is sequestered by an intricate hydrogen bond networks and covalently binds to the conserved catalytic Lys263 to form a reactive Schiff base [186].…”