Jonathan M Mudry1, Petter S Alm2, Sophie Erhardt3, Michel Goiny3, Tomas Fritz4, Kenneth Caidahl1, Juleen R Zierath1,2, Anna Krook5, Harriet Wallberg-Henriksson2. 1. Department of Molecular Medicine and Surgery, Integrative Physiology, Karolinska Institutet, Stockholm, Sweden. 2. Department of Physiology and Pharmacology, Integrative Physiology, Karolinska Institutet, Stockholm, Sweden. 3. Department of Physiology and Pharmacology, Neuropsychoimmunology, Karolinska Institutet, Stockholm, Sweden. 4. Centre for Family and Community Medicine, Karolinska Institutet, Huddinge, Sweden. 5. Department of Physiology and Pharmacology, Integrative Physiology, Karolinska Institutet, Stockholm, Sweden. Anna.Krook@ki.se.
Abstract
BACKGROUND: Systemic kynurenine levels are associated with resistance to stress-induced depression and are modulated by exercise. Tryptophan is a precursor for serotonin and kynurenine synthesis. Kynurenine is transformed into the neuroprotective catabolite kynurenic acid by kynurenine aminotransferases (KATs). PGC-1α1 increases KAT mRNA and induces kynurenic acid synthesis. We tested the hypothesis that skeletal muscle PGC-1α1/KAT-kynurenine pathway is altered by exercise and type 2 diabetes. METHOD: Skeletal muscle and plasma from men with normal glucose tolerance (n = 12) or type 2 diabetes (n = 12) was studied at rest, after acute exercise and during recovery. Tryptophan, Kynurenine and kynurenic acid plasma concentration were measured as well as mRNA of genes related to exercise and kynurenine metabolism. RESULTS: mRNA expression of KAT1, KAT2 and PPARα was modestly reduced in type 2 diabetic patients. In response to exercise, mRNA expression of KAT4 decreased and PGC-1α1 increased in both groups. Exercise increased plasma kynurenic acid and reduced kynurenine in normal glucose tolerance and type 2 diabetic participants. Plasma tryptophan was reduced and the ratio of [kynurenic acid] * 1000/[kynurenine] increased in both groups at recovery, suggesting an improved balance between neurotoxic and neuroprotective influences. Tryptophan and kynurenine correlated with body mass index, suggesting a relationship with obesity. CONCLUSIONS: Acute exercise directly affects circulating levels of tryptophan, kynurenine and kynurenic acid, providing a potential mechanism for the anti-depressive effects of exercise. Furthermore, exercise-mediated changes in kynurenine metabolism are preserved in type 2 diabetic patients.
BACKGROUND: Systemic kynurenine levels are associated with resistance to stress-induced depression and are modulated by exercise. Tryptophan is a precursor for serotonin and kynurenine synthesis. Kynurenine is transformed into the neuroprotective catabolitekynurenic acid by kynurenine aminotransferases (KATs). PGC-1α1 increases KAT mRNA and induces kynurenic acid synthesis. We tested the hypothesis that skeletal muscle PGC-1α1/KAT-kynurenine pathway is altered by exercise and type 2 diabetes. METHOD: Skeletal muscle and plasma from men with normal glucose tolerance (n = 12) or type 2 diabetes (n = 12) was studied at rest, after acute exercise and during recovery. Tryptophan, Kynurenine and kynurenic acid plasma concentration were measured as well as mRNA of genes related to exercise and kynurenine metabolism. RESULTS: mRNA expression of KAT1, KAT2 and PPARα was modestly reduced in type 2 diabeticpatients. In response to exercise, mRNA expression of KAT4 decreased and PGC-1α1 increased in both groups. Exercise increased plasma kynurenic acid and reduced kynurenine in normal glucose tolerance and type 2 diabeticparticipants. Plasma tryptophan was reduced and the ratio of [kynurenic acid] * 1000/[kynurenine] increased in both groups at recovery, suggesting an improved balance between neurotoxic and neuroprotective influences. Tryptophan and kynurenine correlated with body mass index, suggesting a relationship with obesity. CONCLUSIONS: Acute exercise directly affects circulating levels of tryptophan, kynurenine and kynurenic acid, providing a potential mechanism for the anti-depressive effects of exercise. Furthermore, exercise-mediated changes in kynurenine metabolism are preserved in type 2 diabeticpatients.
Authors: David G Lassiter; Rasmus J O Sjögren; Brendan M Gabriel; Anna Krook; Juleen R Zierath Journal: Mol Metab Date: 2018-07-25 Impact factor: 7.422
Authors: Tomasz Saran; Monika Turska; Tomasz Kocki; Magdalena Zawadka; Grzegorz Zieliński; Waldemar A Turski; Piotr Gawda Journal: Sci Rep Date: 2021-05-27 Impact factor: 4.379