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- Agudelo, LZ, et al.
(författare)
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Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2767-
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Tidskriftsartikel (refereegranskat)abstract
- The coactivator PGC-1α1 is activated by exercise training in skeletal muscle and promotes fatigue-resistance. In exercised muscle, PGC-1α1 enhances the expression of kynurenine aminotransferases (Kats), which convert kynurenine into kynurenic acid. This reduces kynurenine-associated neurotoxicity and generates glutamate as a byproduct. Here, we show that PGC-1α1 elevates aspartate and glutamate levels and increases the expression of glycolysis and malate-aspartate shuttle (MAS) genes. These interconnected processes improve energy utilization and transfer fuel-derived electrons to mitochondrial respiration. This PGC-1α1-dependent mechanism allows trained muscle to use kynurenine metabolism to increase the bioenergetic efficiency of glucose oxidation. Kat inhibition with carbidopa impairs aspartate biosynthesis, mitochondrial respiration, and reduces exercise performance and muscle force in mice. Our findings show that PGC-1α1 activates the MAS in skeletal muscle, supported by kynurenine catabolism, as part of the adaptations to endurance exercise. This crosstalk between kynurenine metabolism and the MAS may have important physiological and clinical implications.
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| 7. |
- Krusnauskas, R, et al.
(författare)
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Response to Three Weeks of Sprint Interval Training Cannot Be Explained by the Exertional Level
- 2020
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Ingår i: Medicina (Kaunas, Lithuania). - : MDPI AG. - 1648-9144. ; 56:8
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: The all-out mode of sprint interval training (SIT) has been shown to be an efficient method for improving sports performance, exercise capacity, and aerobic fitness. Although the benefits of SIT are well described, the mechanisms underlying the different degrees of response remain largely unexplored. We aimed to assess the effects of exertion on the responsiveness to SIT. Materials and Methods: The participants were 28 young untrained men (mean ± SD age 25.7 ± 6.03 years) who exhibited either a large or small increase in Wingate test average power in response to nine SIT sessions performed over three weeks. Each training session comprised four–six bouts of 30 s all-out cycling interspaced with 4 min of rest. Individual responses were assessed using heart rate (HR) during exercise for all nine sessions, as well as blood lactate concentration up to 1 h, and the decrement in maximal voluntary knee extension torque (MVC) up to 24 h after the first and last training sessions. Peak oxygen uptake (VO2peak) and maximum HR were measured before and after training during an incremental cycling test to exhaustion. Results: Although all participants showed benefits of SIT such as increased VO2peak, the increase in anaerobic cycling power varied between participants. We identified 17 high responders and nine low responders, whose average power outputs were 0.80 ± 0.22 and 0.22 ± 0.19 W/kg, respectively. The HR achieved during any of the training sessions did not differ between high and low responders. The lactate kinetics did not differ between groups before and after the intervention. Training resulted in a more rapid recovery of MVC without any discernible differences between the high and low responders. Conclusion: The differences in the responses to SIT are not dependent on the exertion level during training.
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| 8. |
- Schlittler, M, et al.
(författare)
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Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans
- 2016
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 310:10, s. C836-C840
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that exercise protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the kynurenine metabolism away from the neurotoxic kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present study, we investigated the effect of exercise on kynurenine metabolism in humans. KAT gene and protein expression was increased in the muscles of endurance-trained subjects compared with untrained subjects. Endurance exercise caused an increase in plasma KYNA within the first hour after exercise. In contrast, a bout of high-intensity eccentric exercise did not lead to increased plasma KYNA concentration. Our results show that regular endurance exercise causes adaptations in kynurenine metabolism which can have implications for exercise recommendations for patients with depressive disorder.
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| 9. |
- Venckunas, T, et al.
(författare)
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Adding High-Intensity Interval Training to Classical Resistance Training Does Not Impede the Recovery from Inactivity-Induced Leg Muscle Weakness
- 2023
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Ingår i: Antioxidants (Basel, Switzerland). - : MDPI AG. - 2076-3921. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Inactivity is known to induce muscle weakness, and chronically increased levels of reactive oxygen species (ROS) are proposed to have a central causative role in this process. Intriguingly, high-intensity interval training (HIIT), which involves bursts of high ROS production, can have positive effects in pathological conditions with chronically increased ROS. Here, young male volunteers were exposed to 3 weeks of unloading of the dominant leg followed by 3 weeks of resistance training without (Ctrl group) or with the addition of all-out cycling HIIT. Changes in muscle thickness were assessed by ultrasonography, and contractile function was studied by measuring the torque during maximal voluntary contractions (MVC). The results show an ~6% decrease in vastus lateralis thickness after the unloading period, which was fully restored after the subsequent training period in both the Ctrl and HIIT groups. MVC torque was decreased by ~11% after the unloading period and recovered fully during the subsequent training period in both groups. All-out cycling performance was improved by the 3 weeks of HIIT. In conclusion, the decline in muscle size and function after 3 weeks of unloading was restored by 3 weeks of resistance training regardless of whether it was combined with HIIT.
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