Exercise-mediated improvement of depression in patients with gastro-esophageal junction cancer is linked to kynurenine metabolism

Herrstedt, Anita; Bay, Marie Lund; Simonsen, Carsten; Sundberg, Anna; Egeland, Charlotte; Thorsen-Streit, Sarah; Djurhuus, Sissal Sigmundsdóttir; Ueland, Per Magne; Midttun, Øivind; Pedersen, Bente Klarlund; Svendsen, Lars Bo; Heer, Pieter de; Christensen, Jesper; Højman, Pernille

doi:10.1080/0284186x.2018.1558371

Cited by 23 publications

(35 citation statements)

References 30 publications

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“…It is noteworthy that the results obtained by both methods were similar, at least when considering the direction and magnitude of changes in sweat composition. Moreover, the results obtained correspond well with data obtained by other researchers investigating changes of kynurenines in blood 6 , 34 , 40 – 43 , 47 . Therefore there is reason to conclude that the measurement of TRP, KYN and KYNA in sweat may have the diagnostic potential, and may also help to establish an exercise regime appropriate for the age, gender, and health status of rehabilitation participant.…”

Section: Discussionsupporting

confidence: 90%

Effect of 4-week physical exercises on tryptophan, kynurenine and kynurenic acid content in human sweat

Saran

Turska

Kocki

et al. 2021

Sci Rep

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The aim of the study was the detection of TRP, kynurenine (KYN), and kynurenic acid (KYNA) in human sweat, and determining whether physical activity affects their content in this secrete. Two different methods were used simultaneously—collection of sweat by means of an absorption pad from the inter scapular region, and collection of a drop of sweat from the region of the forehead. Quantitative determinations of TRP, KYN and KYNA were performed using high performance liquid chromatography with ultraviolet and fluorescence detection. Determinations of sodium was carried out by the method of inductively coupled plasma collision/reaction cell ionization mass spectrophotometry. It was found that physical exercises evoked a decrease in the amount of KYN, and an increase in the amount of KYNA in sweat recorded on day 14, but not on day 28 of training. It appears that physical exercises result in a long-term increase in the kynurenine transaminase activity responsible for the formation of KYNA from KYN. Based on this results, it can be suggested that measurement of TRP, KYN and KYNA in sweat may have diagnostic potential and may help to establish an exercise regime appropriate for the age, gender and health status of rehabilitation patients.

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Section: Discussionsupporting

confidence: 90%

Effect of 4-week physical exercises on tryptophan, kynurenine and kynurenic acid content in human sweat

Saran

Turska

Kocki

et al. 2021

Sci Rep

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“…Moreover, QUINA levels were significantly elevated in the urine of breast cancer patients in comparison to healthy women (Figure 1), which likely is a direct consequence of the enhanced TRP degradation in these patients. Elevated QUINA levels and QUINA/KYNA ratios in patients may also be the consequence of an inflammation driven induction of kynurenine 3-monooxygenase (KMO) (39). Comparison of the effects of resistance exercise between breast cancer patients (IG) and healthy women (HIG) revealed that while urine QUINA levels and the QUINA/KYNA ratio were reduced in the healthy subjects (HIG), breast cancer patients (IG) showed reduced KYNA/KYN ratios and elevated QUINA/KYNA ratios after completion of the 12-week exercise training (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Resistance Exercise Reduces Kynurenine Pathway Metabolites in Breast Cancer Patients Undergoing Radiotherapy

et al. 2019

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Purpose: Evidence from preclinical studies and trials in healthy volunteers suggests that exercise may modulate the levels of tryptophan (TRP) metabolites along the kynurenine (KYN) pathway. As KYN and downstream KYN metabolites are known to promote cancer progression by inhibiting anti-tumor immune responses and by promoting the motility of cancer cells, we investigated if resistance exercise can also control the levels of KYN pathway metabolites in breast cancer patients undergoing radiotherapy (NCT01468766).Patients and Methods: Chemotherapy-naïve breast cancer patients (n = 96) were either randomized to an exercise/intervention group (IG) or a control group (CG). The IG participated in a 12-week supervised progressive resistance exercise program twice a week, whereas the CG received a supervised relaxation program. Serum levels of TRP and KYN as well as urine levels of kynurenic acid (KYNA) and neurotoxic quinolinic acid (QUINA) were assessed before (t0), after radiotherapy, and mid-term of the exercise intervention (t1) and after the exercise intervention (t2). Additionally, 24 healthy women (HIG) participated in the exercise program to investigate potential differences in its effects on KYN metabolites in comparison to the breast cancer patients.Results: At baseline (t0) the breast cancer patients showed a significantly elevated serum KYN/TRP ratio and urine QUINA/KYNA ratio, as well as increased urine QUINA levels in comparison to the healthy women. In response to exercise the healthy women and the breast cancer patients differed significantly in the levels of urine QUINA and the QUINA/KYNA ratio. Most importantly, serum KYN levels and the KYN/TRP ratio were significantly reduced in exercising patients (IG) compared to non-exercising patients (CG) both at t1 and t2.Conclusion: Resistance exercise may represent a potent non-pharmacological avenue to counteract an activation of the KYN pathway in breast cancer patients undergoing radiotherapy.

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“…In addition, in mice with PGC1α being overexpressed or knocked down in muscle tissue specifically, KAT expression is increased and decreased, respectively, indicating the importance of PGC1α in KAT regulation [16]. In a recent study of cancer patients, an exercise-mediated improvement in depression was also linked to KYN metabolism [20]. We cannot rule out that other organs or tissues are involved in the elevated circulating KYN levels in COPD as well, but these findings suggest that exercise training, currently a core component of pulmonary rehabilitation to treat muscle dysfunction in COPD [21], by restoring muscle PGC1α signaling and KAT4 expression, might also be beneficial in the treatment of mental comorbidities.…”

Section: Discussionmentioning

confidence: 99%

Impaired Skeletal Muscle Kynurenine Metabolism in Patients with Chronic Obstructive Pulmonary Disease

Gosker

Clarke

Theije

et al. 2019

JCM

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Background: Loss of peripheral muscle oxidative phenotype, cognitive impairment, and depression are well-recognized systemic manifestations of chronic obstructive pulmonary disease (COPD). Kynurenine (KYN), known to be associated with disturbed mental health, can be metabolized in muscle by kynurenine aminotransferases (KAT) 1–4. These KATs are regulated by peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PGC1α). We hypothesize that impaired PGC1α signaling in COPD is associated with reduced muscle KAT expression and increased KYN plasma levels. Methods: Retrospective collected and metabolically phenotyped muscle tissue and blood obtained from 29 well-characterized COPD patients and 15 healthy controls were analyzed. KYN was measured in plasma and KAT1–4 expression and major constituents of PGC1α signaling were assessed in quadriceps muscle biopsies. Results: Circulating KYN levels were increased in COPD. Furthermore, both gene and protein expression levels of KAT4 were reduced in muscle tissue from COPD patients. Finally, in the whole group (even when controlled for airflow obstruction) and in each subgroup separately, KAT4 gene expression correlated significantly with constituents of the PGC1α signaling pathway. Conclusions: These data support our hypothesis that KYN plasma levels are elevated in COPD through impaired KYN clearance in muscle. Our findings show a pathway via which exercise training and/or nutritional modulation may improve physical and mental health in COPD patients.

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Exercise-mediated improvement of depression in patients with gastro-esophageal junction cancer is linked to kynurenine metabolism

Cited by 23 publications

References 30 publications

Effect of 4-week physical exercises on tryptophan, kynurenine and kynurenic acid content in human sweat

Effect of 4-week physical exercises on tryptophan, kynurenine and kynurenic acid content in human sweat

Resistance Exercise Reduces Kynurenine Pathway Metabolites in Breast Cancer Patients Undergoing Radiotherapy

Impaired Skeletal Muscle Kynurenine Metabolism in Patients with Chronic Obstructive Pulmonary Disease

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