While moderate acute exercise has been associated with strong anti-inflammatory mechanisms, strenuous exercise has been linked to deleterious inflammatory perturbations. It is therefore fundamental to elucidate the mechanisms that regulate the exercise-induced inflammatory cascade. Information on novel regulators such as circulating inflammatory microRNAs (c-inflammamiRs) is incomplete. In this study, we evaluated the response of a panel of c-inflammamiRs to different doses of acute aerobic exercise. We first studied the exercise-induced inflammatory cascade in serum samples of nine active middle-aged males immediately before and after (0 h, 24 h, 72 h) 10-km, half-marathon, and marathon races. Next, we analyzed the circulating profile of 106 specific c-inflammamiRs immediately before) and after (0 h, 24 h) 10-km (low inflammatory response) and marathon (high inflammatory response) races. Analysis of classical inflammatory parameters revealed a dose-dependent effect of aerobic exercise on systemic inflammation, with higher levels detected after marathon. We observed an increase in miR-150-5p immediately after the 10-km race. Levels of 12 c-inflammamiRs were increased immediately after the marathon (let-7d-3p, let-7f-2-3p, miR-125b-5p, miR-132-3p, miR-143-3p, miR-148a-3p, miR-223-3p, miR-223-5p, miR-29a-3p, miR-34a-5p, miR-424-3p, and miR-424-5p). c-inflammamiRs returned to basal levels after 24 h. Correlation and in silico analyses supported a close association between the observed c-inflammamiR pattern and regulation of the inflammatory process. In conclusion, we found that different doses of acute aerobic exercise induced a distinct and specific c-inflammamiR response, which may be associated with control of the exercise-induced inflammatory cascade. Our findings point to c-inflammamiRs as potential biomarkers of exercise-induced inflammation, and hence, exercise dose.

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Considering that hyperhomocysteinemia is an independent risk factor for cardiovascular disease, the purpose of this study was to determine the kinetics of serum homocysteine (tHcy) and the vitamins involved in its metabolism (folates, B12, and B6) in response to acute exercise at different intensities. Eight sedentary males (18–27 yr) took part in the study. Subjects were required to complete two isocaloric (400 kcal) acute exercise trials on separate occasions at 40% (low intensity, LI) and 80% VO2peak (high intensity, HI). Blood samples were drawn at different points before (pre4 and pre0 h), during (exer10, exer20, exer30, exer45, and exer60 min), and after exercise (post0, post3, and post19 h). Dietary, genetic, and lifestyle factors were controlled. Maximum tHcy occurred during exercise, both at LI (8.6 (8.0–10.1) µmol/L, 9.3% increase from pre0) and HI (9.4 (8.2–10.6) µmol/L, 25.7% increase from pre0), coinciding with an accumulated energy expenditure independent of the exercise intensity. From this point onwards tHcy declined until the cessation of exercise and continued descending. At post19, tHcy was not different from pre-exercise values. No values of hyperhomocysteinemia were observed at any sampling point and intensity. In conclusion, acute exercise in sedentary individuals, even at HI, shows no negative effect on tHcy when at least 400 kcal are spent during exercise and the nutritional status for folate, B12, and B6 is adequate, since no hyperhomocysteinemia has been observed and basal concentrations were recovered in less than 24 h. This could be relevant for further informing healthy exercise recommendations.

The systemic response to exercise is dose‐dependent and involves a complex gene expression regulation and cross‐talk between tissues. This context ARISES the need for analyzing the influence of exercise dose on the profile of circulating microRNAs (c‐miRNAs), as emerging posttranscriptional regulators and intercellular communicators. Thus, we hypothesized that different exercise doses will determine specific c‐miRNA signatures that will highlight its potential as exercise dose biomarker. Nine active middle‐aged males completed a 10‐km race (10K), a half‐marathon (HM), and a marathon (M). Blood samples were collected immediately before and after races. Plasma RNA was extracted, and a global screening of 752 microRNAs was analyzed using RT‐qPCR. Three different c‐miRNA profiles were defined according to the three doses. In 10K, 14 c‐miRNAs were found to be differentially expressed between pre‐ and post‐exercise, 13 upregulated and 1 downregulated. Regarding HM, 13 c‐miRNAs were found to be differentially modulated, in all the cases upregulated. A total of 28 c‐miRNAs were found to be differentially expressed in M, 21 overexpressed and 7 repressed after this race. We had also found 3 common c‐miRNAs between 10K and M and 2 common c‐miRNAs between 10K and HM. In silico analysis supported a close association between exercise dose c‐miRNA profiles and cellular pathways linked to energy metabolism and cell cycle. In conclusion, we have observed that different exercise doses induced specific c‐miRNA profiles. So, our results point to c‐miRNAs as emerging exercise dose biomarkers and as one of regulatory mechanisms modulating the response to endurance exercise.

Background and aims:The association between bone turnover markers and bone mass in adolescence is not clear. We aimed to evaluate the associations between bone turnover markers and bone mineral content (BMC), density (BMD) and area (BMA). Subjects: A total of 56 adolescents (25 boys, 12.5 -17.5 years) participated in the study. Methods: Bone mass and physical activity (PA) were measured using dual energy X-ray absorptiometry and accelerometers. Osteocalcin and amino-terminal propeptide of type I procollagen (PINP), as markers of bone formation, and β -isomer of the C-terminal telopeptide of type I collagen, as marker of bone resorption were also measured. Sexual maturation, weight, height and average PA were considered as confounders. Results: Positive correlations (Pearson) were observed among the three bone turnover markers (r = 0.7 -0.9). Stepwise multiple linear regression analyses showed that PINP was strong and negatively associated with BMC, BMD and BMA in girls, explaining 24.9 % of the variance in BMC, 25.6 % in BMD and 16.3 % in BMA. Conclusion: PINP is a strong predictor of bone related variables in pubertal girls.