Effect of a Single Bout of Aerobic Exercise on Kynurenine Pathway Metabolites and Inflammatory Markers in Prostate Cancer Patients—A Pilot Randomized Controlled Trial

Schenk, Alexander; Esser, Tobias; Knoop, André; Thevis, Mario; Herden, Jan; Heidenreich, Axel; Bloch, Wilhelm; Joisten, Niklas; Zimmer, Philipp

doi:10.3390/metabo11010004

Cited by 8 publications

(6 citation statements)

References 56 publications

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“…Although we did not measure peripheral or central serotonin levels, it is tempting to speculate that the TRP supplementation could have affected serotonin levels, and thus increasing wheel running activity. On the other hand, the number of studies addressing the effects of exercise on TRP catabolism through the KP are constantly increasing [ 14 , 15 , 25 , 26 , 27 , 28 , 29 ]. Once again, it is important to consider how the studies were planned when comparing data from the different sources.…”

Section: Discussionmentioning

confidence: 99%

Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans

et al. 2021

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The kynurenine pathway of tryptophan (TRP) degradation (KP) generates metabolites with effects on metabolism, immunity, and mental health. Endurance exercise training can change KP metabolites by changing the levels of KP enzymes in skeletal muscle. This leads to a metabolite pattern that favors energy expenditure and an anti-inflammatory immune cell profile and reduces neurotoxic metabolites. Here, we aimed to understand if TRP supplementation in untrained vs. trained subjects affects KP metabolite levels and biological effects. Our data show that chronic TRP supplementation in mice increases all KP metabolites in circulation, and that exercise reduces the neurotoxic branch of the pathway. However, in addition to increasing wheel running, we did not observe other effects of TRP supplementation on training adaptations, energy metabolism or behavior in mice. A similar increase in KP metabolites was seen in trained vs. untrained human volunteers that took a TRP drink while performing a bout of aerobic exercise. With this acute TRP administration, TRP and KYN were higher in the trained vs. the untrained group. Considering the many biological effects of the KP, which can lead to beneficial or deleterious effects to health, our data encourage future studies of the crosstalk between TRP supplementation and physical exercise.

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Section: Discussionmentioning

confidence: 99%

Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans

et al. 2021

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“…Logically following time motion analysis showing that backcourt players spend more time doing dynamic movements during the game, the coinciding metabolomic analysis indicates a greater reliance of aerobic metabolism compared to frontcourts. More specifically, we find higher pyruvate concentration and lower lactic acid in backcourt players which indicate that most of the produced pyruvate entered the Krebs cycle and was utilized in the aerobic metabolism (Mougios 2019;Schenk et al, 2021). A higher Krebs cycle activity is also supported by higher succinic acid and citric acid (i.e., Krebs cycle mediators) (Blackburn et al, 2020).…”

Section: Discussionmentioning

confidence: 72%

Using Metabolomics to Differentiate Player Positions in Elite Male Basketball Games: A Pilot Study

Khoramipour

Gaeini

Shirzad

et al. 2021

Front. Mol. Biosci.

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Purpose: The current study compared metabolic profiles and movement patterns between different player positions and explored relationships between indicators of internal and external loads during elite male basketball games.Methods: Five main players from 14 basketball teams (n = 70) were selected as subjects and defined as backcourt (positions 1–3) or frontcourt (positions 4–5) players. Video-based time motion analysis (VBTMA) was performed based on players’ individual maximal speeds. Movements were classified into high and low intensity running with and without ball, high and low intensity shuffling, static effort and jumps. Saliva samples were collected before and after 40-min basketball games with metabolomics data being analyzed by multivariate statistics. Independent t-tests were used to compare VBTMA.Results: Frequency, duration, and distance of high and low intensity running and -shuffling were higher in backcourt players, whereas static effort duration and frequency as well as jump frequency were higher in frontcourt players (all p ≤ 0.05). The levels of taurine, succinic acid, citric acid, pyruvate, glycerol, acetoacetic acid, acetone, and hypoxanthine were higher in backcourt players, while lactate, alanine, 3-methylhistidine were higher and methionine was lower in frontcourt players (all p < 0.05). High intensity running with ball was significantly associated by acetylecholine, hopoxanthine, histidine, lactic acid and leucine in backcourt players (p < 0.05).Conclusion: We demonstrate different metabolic profiles of backcourt and frontcourt players during elite male basketball games; while aerobic metabolic changes are more present in backcourt players, frontcourt players showed lager changes in anaerobic metabolic pathways due to more static movements.

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“…In fact, Trp catabolism of tumor cells is increasingly being recognized as an essential participant in regulating tumor progression [29]. A newly study provided evidence that activation of Kyn associated signaling pathway might e ciently promote the tumor progression and mortality in prostatic cancer [30]. However, the potential correlation between Trp metabolism and prostatic cancer chemoresistance remained poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Tryptophan Metabolism Induced by TDO2 Promotes Prostatic Cancer Chemotherapy Resistance in a Ahr/C-Myc Dependent Manner

Zhao

Zhang

et al. 2021

Preprint

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Background: Tumor cells exhibit enhanced metabolism of nutrients to satisfy the demand of sustained proliferation in vivo. Seminal reports have presented evidence that tryptophan (Trp) metabolic reprogramming induced by aberrant indoleamine 2,3-dioxygenases could promote tumor development in several cancer types. However, the underlying mechanism of Trp metabolism associated tumor progression is not fully understood.Materials and methods: Prostatic cell lines LNCaP and VCaP were purchased from the Cell Bank of the Chinese Academy of Sciences (China). Human prostatic tumor tissue samples were obtained from the Tongji Hospital. Female NOD-SCID mice (6~8 weeks) were purchased from Huafukang Co. (China) and raised in SPF room. Commercial kits and instruments were used for cell apoptosis analysis, real-time PCR, western blotting, ELISA analysis and other experiments.Result: Comparing the tumor tissues from prostatic cancer patients, we found elevated expression of tryptophan 2，3-dioxygenase 2 (TDO2), and elevated Trp metabolism in chemo-resistant tumor tissues. In vitro, overexpression of TDO2 significantly promoted the Trp metabolism in prostatic cancer cell lines LNCaP and VCap, resulting in the multidrug resistance development. Mechanistically, we demonstrated that Trp metabolite kynurenine (Kyn) promoted the upregulation and nuclear translocation of transcription factor aryl hydrocarbon receptor (AhR). Subsequently, AhR collaborated with NF-κB to facilitate the activation of c-Myc. In turn, c-Myc promoted the up-regulation of ATP-binding cassette (ABC) transporters and Trp transporters, thereby contributing to chemoresistance and strengthened Trp metabolism in prostatic cancer. Interrupt of Trp/TDO2/Kyn/AhR/c-Myc loop with c-Myc inhibitor Mycro-3 efficiently suppressed the chemoresistance and improved the outcome of chemotherapy, which described a new strategy in clinical prostatic cancer treatment. Conclusion：Our study demonstrates that elevated TOD2 expression promoted Trp metabolism and metabolite Kyn production, thus resulting in the activation of AhR/c-Myc/ABC-SLC transporters signaling pathway. Interrupt of Trp metabolism/c-Myc loop efficiently suppressed the drugs resistance induced by TDO2, which represented potential target to improve the outcome in drug-resistant prostatic cancer treatment.

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Effect of a Single Bout of Aerobic Exercise on Kynurenine Pathway Metabolites and Inflammatory Markers in Prostate Cancer Patients—A Pilot Randomized Controlled Trial

Cited by 8 publications

References 56 publications

Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans

Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans

Using Metabolomics to Differentiate Player Positions in Elite Male Basketball Games: A Pilot Study

Tryptophan Metabolism Induced by TDO2 Promotes Prostatic Cancer Chemotherapy Resistance in a Ahr/C-Myc Dependent Manner

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