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Modulation of testing conditions such as resting lactate (Larest) levels or carbohydrate intake may affect the calculation of the maximal glycolytic rate (νLa.max). To evaluate the impact of elevated Larest as well as reduced and increased carbohydrate availability on νLa.max in running sprints (RST), twenty‐one participants completed five 15‐s RST tests on a running track under five different conditions: (I). baseline: Larest ≤1.5 mmol·L−1; (II). Lactate+: Larest ≥2.5 mmol·L−1; (III). CHO−: carbohydrate intake: ≤ 1 g·kg−1 BW d−1 for 3 days; (IV). CHO+: carbohydrate intake: ≥ 9 g·kg−1 BW d−1 for one day; and (V). acuteCHO: 500 mL glucose containing beverage consumed before RST. νLa.max was significantly reduced in lactate+ and CHO− conditions compared to the baseline RST, due to a reduction in the arithmetic mean delta (∆) between Lapeak and Larest lactate concentration (Lapeak, mmol · L−1). AcuteCHO led to an increase in Larest compared to baseline, CHO− and CHO+ with a high interindividual variability but did not significantly reduce νLa.max. Therefore, avoiding low carbohydrate nutrition before νLa.max testing, along with carefully adjusting Larest to below ≤1.5 mmol·L‐1, is crucial to prevent the unintentional underestimation of νLa.max. [ABSTRACT FROM AUTHOR]

The kynurenine pathway (KP) of tryptophan degradation generates several metabolites such as kynurenine (KYN) or kynurenic acid (KA) that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an acute exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral blood mononuclear cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise. Exercise effects on both, kynurenic acid and AHR activation in PBMCs were greater in response to high-intensity interval exercise (HIIE) (50 min, six 3-min intervals at 90% V̇ o 2peak, and 3-min intervals at 50% V̇ o 2peak in between) compared with workload-matched moderate-intensity continuous exercise (MICE) (50 min). In conclusion, these data indicate a novel mechanistic link in how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases. NEW & NOTEWORTHY: The findings of this study show that acute endurance exercise activates a receptor that has been described to integrate metabolic signals into the immune system. We uncover a potential mechanistic link on how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases and of relevance for other cell types. [ABSTRACT FROM AUTHOR]

MicroRNA-1 (miR-1) is the most abundant miRNA in adult skeletal muscle. To determine the function of miR-1 in adult skeletal muscle, we generated an inducible, skeletal muscle-specific miR-1 knockout (KO) mouse. Integration of RNA-sequencing (RNA-seq) data from miR-1 KO muscle with Argonaute 2 enhanced crosslinking and immunoprecipitation sequencing (AGO2 eCLIP-seq) from human skeletal muscle identified miR-1 target genes involved with glycolysis and pyruvate metabolism. The loss of miR-1 in skeletal muscle induced cancer-like metabolic reprogramming, as shown by higher pyruvate kinase muscle isozyme M2 (PKM2) protein levels, which promoted glycolysis. Comprehensive bioenergetic and metabolic phenotyping combined with skeletal muscle proteomics and metabolomics further demonstrated that miR-1 KO induced metabolic inflexibility as a result of pyruvate oxidation resistance. While the genetic loss of miR-1 reduced endurance exercise performance in mice and in C. elegans, the physiological down-regulation of miR-1 expression in response to a hypertrophic stimulus in both humans and mice causes a similar metabolic reprogramming that supports muscle cell growth. Taken together, these data identify a novel post-translational mechanism of adult skeletal muscle metabolism regulation mediated by miR-1.

Skeletal muscle is a target of contraction-induced loading (CiL), leading to protein unfolding or cellular perturbations, respectively. While cytoskeletal desmin is responsible for ongoing structural stabilization, in the immediate response to CiL, alpha-crystallin B (CRYAB) is phosphorylated at serine 59 ( p CRYAB S59 ) by P38, acutely protecting the cytoskeleton. To reveal adaptation and deadaptation of these myofibrillar subsystems to CiL, we examined CRYAB, P38, and desmin regulation following resistance exercise at diverse time points of a chronic training period. Mechanosensitive JNK phosphorylation ( p JNK T183/Y185 ) was determined to indicate the presence of mechanical components in CiL. Within 6 wk, subjects performed 13 resistance exercise bouts at the 8-12 repetition maximum, followed by 10 days detraining and a final 14th bout. Biopsies were taken at baseline and after the 1st, 3rd, 7th, 10th, 13th, and 14th bout. To assess whether potential desensitization to CiL can be mitigated, one group trained with progressive and a second with constant loading. As no group differences were found, all subjects were combined for statistics. Total and phosphorylated P38 was not regulated over the time course. p CRYAB S59 and p JNK T183/Y185 strongly increased following the unaccustomed first bout. This exercise-induced p CRYAB S59 / p JNK T183/Y185 increase disappeared with the 10th until 13th bout. As response to the detraining period, the 14th bout led to a renewed increase in p CRYAB S59 . Desmin content followed p CRYAB S59 inversely, i.e., was up- when p CRYAB S59 was downregulated and vice versa. In conclusion, the p CRYAB S59 response indicates increase and decrease in resistance to CiL, in which a reinforced desmin network could play an essential role by structurally stabilizing the cells.