Physical Exercise as Kynurenine Pathway Modulator in Chronic Diseases: Implications for Immune and Energy Homeostasis, 2020, Joisten et al

Andy · Jul 21, 2020

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+) and finally suggest how these modulations may contribute to exercise-induced benefits in the prevention and treatment of chronic diseases.
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Open access, https://journals.sagepub.com/doi/10.1177/1178646920938688

Snowdrop · Jul 21, 2020

Recently, physical exercise has been shown to impact the KYN pathway regulation in response to both single bouts of (acute) exercise and long-term interventions of repetitive exercise bouts (chronic training).
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What's not clear to me from skimming some of the write up is, are they referring to exercise done by healthy subjects and applying it to chronic illness?

Can anyone enlighten me?

Hoopoe · Jul 21, 2020

How this relates to the metabolic trap hypothesis:

Under normal physiological conditions, the KYN pathway is mainly regulated by the enzyme tryptophan 2,3 dioxygenase (TDO), which mediates the conversion of tryptophan to KYN (representing the initial step of the KYN pathway). However, in the presence of local or systemic inflammatory conditions, the activity of the TDO isoenzymes indoleamine 2,3 (IDO) 1 and 2 can increase substantially, thereby leading to an activation of the KYN pathway.
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Several studies showed an initial activation of the KYN pathway in response to acute exercise as indicated by a decrease in TRP and an increase in KYN measured in human serum/plasma.
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There is a strong rationale suggesting that the observed initial activation of the KYN pathway as well as the increase in the metabolic flux towards QA is driven by immune activation as they appear transiently during and after single bouts of exercise. Immune activation during and after acute exercise has especially been described as an elevation in inflammatory cytokines such as interleukin-6 (IL-6).24,25 Indeed, primarily interferon-γ (IFN-γ) and also other inflammatory cytokines (eg, IL-6) are known to induce IDO1, IDO2, and KMO,5 thereby creating a solid link to an IDO-mediated upregulation of the KYN pathway and an increased degradation of KYN to QA in response to acute exercise. However, this hypothesis has not yet been investigated in detail and needs to be addressed in future research.
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Snow Leopard · Jul 22, 2020

strategist said: ↑

How this relates to the metabolic trap hypothesis:
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Notably, the assumption is the opposite direction of Phair's metabolic trap hypothesis.

The KYN pathway is deregulated in various chronic diseases, such as different internal (eg, chronic obstructive pulmonary disease,4 diabetes,2 cancer5) or neurological (eg, multiple sclerosis,6 Alzheimer and Parkinson disease7) disorders. When compared with healthy controls, most of these diseases show a persistent overactivation of the KYN pathway as indicated by elevated levels of KYN and the KYN/TRP ratio
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FMMM1 · Jul 30, 2020

Snow Leopard said: ↑

Notably, the assumption is the opposite direction of Phair's metabolic trap hypothesis.
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Haven't checked this but Phair is talking about intracellular tryptophan being elevated and the kynurinine pathway blocked. Is this paper measuring levels of Kynurinine in plasma and if so is there another source of Kynurinine? Also, some cells use IDO2 (potentially trapped) and some don't; think Phair is hypothesising that only some cells will be affected.

I don't have much formal training in this so ----

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Physical Exercise as Kynurenine Pathway Modulator in Chronic Diseases: Implications for Immune and Energy Homeostasis, 2020, Joisten et al

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Physical Exercise as Kynurenine Pathway Modulator in Chronic Diseases: Implications for Immune and Energy Homeostasis, 2020, Joisten et al

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