Acute Increase in Blood αCGRP at Maximal Exercise and Its Association to Cardiorespiratory Fitness, Carbohydrate Oxidation and Work Performed: An Exploratory Study in Young Men

SIMPLE SUMMARY: αCGRP is a neuropeptide that increases in blood during high-intensity exercise in humans. However, the physiological meaning of this molecular response is unknown. Previous experimental works in rodents have related this neuropeptide to several biological processes in the skeletal muscle tissue and cardiorespiratory physiology. Based on the data from these animal studies we hypothesized that in humans αCGRP release during exercise could be similarly associated to metabolic and cardiorespiratory responses. To test this hypothesis, we subjected a sample of physically active young men to an exercise test up to exhaustion while their oxygen uptake (VO(2max)), CO(2) production (VCO(2)), carbohydrate oxidation and performed work were measured. Blood samples were taken before the exercise test, at maximal intensity and after the volunteers have recovered, and the blood concentration of αCGRP was measured. We found that 2/3 of the volunteers responded to maximal exercise with an increase of their blood αCGRP concentration (responders), while the resting 1/3 did not (non-responders). We also found that VO(2max), VCO(2), carbohydrate oxidation and performed work were higher in the responders when compared to the non-responders. Therefore, our observations support that αCGRP release during exercise may be associated to physiological responses related to physical performance. ABSTRACT: This study aimed to explore if the acute variations in plasma concentration of α-calcitonin gene-related peptide (αCGRP) induced by a single maximal exercise bout may be associated to cardiorespiratory fitness and carbohydrate oxidation in humans. Twelve young adult Caucasian men (24.3 ± 0.9 years-old; 179.2 ± 1.9 cm of height; 23.9 ± 0.6 kg·m(−2) body mass index) performed a graded exercise test. A venous catheter was placed before testing, and blood samples were taken at baseline, maximal effort and recovery. αCGRP was measured in plasma using a commercial double-sandwich enzyme-linked-immunoassay. A two-way repeated measurements ANOVA was used to compare the values obtained at baseline, maximal effort and recovery. In the whole sample, αCGRP increased at maximal effort and its concentration correlated directly, albeit non-significantly, with the muscle mass normalised VO(2), VCO(2), carbohydrate oxidation and relative power. Two thirds of the participants showed an increase in αCGRP concentration at maximal effort. Post hoc analysis showed that in these individuals, the muscle mass normalised VO(2), VCO(2), carbohydrate oxidation rate and relative power were higher than in the participants lacking this molecular response. Therefore, our data suggest that (a) a majority of young men respond to exercise with an increase in blood αCGRP concentration; and (b) individuals exhibiting this response also show a higher cardiorespiratory fitness, carbohydrate oxidation and work performed. These findings suggest that this neuropeptide could act as an exerkine with potential effects on physical performance.