Physical Exercise as Kynurenine Pathway Modulator in Chronic Diseases: Implications for Immune and Energy Homeostasis

Abstract

<jats:p> Emerging evidence highlights the substantial role of the kynurenine pathway in various physiological systems and pathological conditions. Physical exercise has been shown to impact the kynurenine pathway in response to both single (acute) and multiple (chronic) exercise training stimuli. In this perspective article, we briefly outline the current knowledge concerning exercise-induced modulations of the kynurenine pathway and discuss underlying mechanisms. Furthermore, we expose the potential involvement of exercise-induced kynurenine pathway modulations on energy homeostasis (eg, through de novo synthesis of NAD<jats:sup>+</jats:sup>) and finally suggest how these modulations may contribute to exercise-induced benefits in the prevention and treatment of chronic diseases. </jats:p>

Investigating novel biomarkers of immune activation and modulation in the context of sedentary behaviour: a multicentre prospective ischemic stroke cohort study

“…We found an inverse association between KA and sedentary behaviour, and the association was strengthened after adjustment for inflammation. KA is metabolised from kynurenine by kynurenine amino transferases (KATs) [ 27 ] and is part of a negative feedback loop where chronic inflammation induces immune tolerance via the aryl hydrocarbon receptor (AhR) and the G-protein-coupled receptor 35 [ 18 , 26 , 27 , 44 , 45 ]. In a recent review, Joisten et al argued for the relevance of KA in disease prevention [ 26 ].…”

“…KA is metabolised from kynurenine by kynurenine amino transferases (KATs) [ 27 ] and is part of a negative feedback loop where chronic inflammation induces immune tolerance via the aryl hydrocarbon receptor (AhR) and the G-protein-coupled receptor 35 [ 18 , 26 , 27 , 44 , 45 ]. In a recent review, Joisten et al argued for the relevance of KA in disease prevention [ 26 ]. KAT expression and activity has been found to be induced by chronic exercise via peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α) and the associated transcription factor, peroxisome proliferator activated receptor alpha (PPARα) [ 28 – 31 ].…”

“…Kynurenic acid (KA), a side-product in the KP, is not an inflammatory biomarker but part of a negative feedback mechanism inducing immune tolerance [ 26 , 27 ]. The role of KA in health and disease is not fully understood [ 26 ] and KA has never been investigated in relation to sedentary behaviour.…”

“…Kynurenic acid (KA), a side-product in the KP, is not an inflammatory biomarker but part of a negative feedback mechanism inducing immune tolerance [ 26 , 27 ]. The role of KA in health and disease is not fully understood [ 26 ] and KA has never been investigated in relation to sedentary behaviour. KA has been found to increase following physical exercise and KA can potentially be one of the molecular links between sedentary behaviour and inflammation [ 22 , 28 – 32 ].…”

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

“…Physical exercise influences the muscle TRP-KYN metabolism and thus energy homeostasis. Intervention through physical exercise program is under thorough study for obesity and chronic illnesses including diseases affecting the CNS [7][8][9].…”