Acute hypertrophic but not maximal strength loading transiently enhances the kynurenine pathway towards kynurenic acid

Abstract

Purpose Due to distinct immuno-and neuro-modulatory properties, growing research interest focuses on exercise-induced alterations of the kynurenine (KYN) pathway in healthy and clinical populations. To date, knowledge about the impact of different acute strength exercise modalities on the KYN pathway is scarce. Therefore, we investigated the acute effects of hypertrophic (HYP) compared to maximal (MAX) strength loadings on the KYN pathway regulation. Methods Blood samples of twelve healthy males (mean age and weight: 23.5 ± 3.2 years; 77.5 ± 7.5 kg) were collected before (T 0), immediately after (T 1), and 1 h after completion (T 2) of HYP (5 sets with 10 repetitions at 80% of 1RM) and MAX (15 sets with 1RM) loadings performed in a randomized cross-over design. Serum concentrations of tryptophan (TRP), KYN, kynurenic acid (KA), and quinolinic acid (QA) were assessed using high-performance liquid chromatography. Results The KA/KYN ratio increased from T 0 to T 1 (p = 0.01) and decreased from T 1 to T 2 (p = 0.011) in HYP, while it was maintained within MAX. Compared to MAX, serum concentrations of KA were greater in HYP at T 1 (p = 0.014). Moreover, the QA/KA ratio was significantly lower in HYP than in MAX at T 1 (p = 0.002). Conclusion Acute HYP loading led to increases in the metabolic flux yielding KA, thereby possibly promoting immunosuppression and neuroprotection. Our findings emphasize the potential of acute HYP exercise as short-term modulator of KYN pathway downstream to KA in healthy males and need to be proven in other samples.

Quantification of Plasma Kynurenine Metabolites Following One Bout of Sprint Interval Exercise

“…23,40,43 One study showed an acute effect of high intensity exercise in healthy subjects, resulting in increased KYNA directly after exercise and then back to baseline after 1 hour. 45 Endurance training also increases plasma QUIN levels, 22,23,43 while resistance exercise does not. 23,43 It is clear from these works that the type of exercise (endurance, resistance or nonendurance) and baseline fitness levels (eg, someone running a marathon 22 or cycling long-distances 43 is well-trained to perform that task) differentially influence metabolism along the kynurenine pathway.…”

“…For instance, in healthy subjects, exercise intensity affects the kynurenine metabolites differently, by increasing KYNA plasma levels after hypertrophic strength loading, but not after maximal strength loading. 45 Irrespective of lab-to-lab variations in methods and design, together, these sometimes-contradictory studies suggest that plasma kynurenine metabolites can change within temporally limited windows and that the direction of change depends on the type, length and intensity of the exercise performed. The current investigation also presents some limitations with respect to the experimental design such as lack of physiological parameters controlling for “all-out” performance and uncontrolled food intake before plasma sampling.…”

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

“…[10][11][12][13][14] Most of these studies investigated severe aerobic exercise as intervention in the form of an incremental exercise test until exhaustion. [11][12][13][14] Furthermore, several studies reported an increased metabolic flux towards KA following acute exercise, 10,[15][16][17] which could possibly be due to an elevation in KAT enzyme expression. Not only the metabolic flux towards KA, but also the major branch of the KYN pathway towards QA can apparently be upregulated after acute exercise.…”

“…Recent results suggest that alterations of KYN pathway metabolites measured in blood serum are of transient nature, and levels return to baseline within 1 hour after exercise cessation. 10,15 Regarding the effects of chronic exercise training on the KYN pathway, existing evidence from human studies is more contradictive compared with effects of acute exercise. Many studies do not show statistical effects on circulating metabolites, [19][20][21] but the design and/or description of the interventions is questionable due to low training frequency/ intensity or lacking information on the applied exercise modalities and adherence.…”

“…Recent results suggest that alterations of KYN pathway metabolites measured in blood serum are of transient nature, and levels return to baseline within 1 hour after exercise cessation. 10,15…”