Whole-blood transcriptome analysis reveals distinct gene expression signatures in paediatric patients with sickle cell anaemia before and after exercise.

Sickle cell anaemia (SCA) patients display elevated levels of circulating pro-inflammatory cytokines and endothelial activation markers compared to healthy peers. The impact of exercise on the pro-inflammatory state in SCA remains unclear. This study aimed to characterize the whole-blood transcriptome profile in response to an acute bout of exercise in paediatric SCA patients. Twenty-three SCA participants (13 ± 3 years, 52% girls) and 17 healthy controls (14 ± 3 years, 29% girls) performed eight 2-min bouts of cycle ergometry interspersed with 1-min rest intervals. Whole-blood transcriptome profile (RNA-seq) was performed before and after exercise. At baseline, gene pathways associated with gas transport in erythrocytes were up-regulated in SCA patients compared to controls. Following exercise, gene pathways associated with innate immunity were altered in both groups. Interaction analyses revealed 160 annotated genes (101 up- and 59 down-regulated) that differentially altered by exercise in SCA patients. Moreover, genes that exhibited a blunted response to exercise in SCA patients were enriched in the IL-17 signalling pathway, suggesting an impaired innate immune response to exercise. This data will contribute to the development of evidence-based exercise prescription guidelines for this patient population.

Exercise Training Attenuates the Muscle Mitochondria Genomic Response to Bed Rest.

PURPOSE: Exercise training during the National Aeronautics and Space Administration (NASA) 70-day bed rest study effectively counteracted the decline in aerobic capacity, muscle mass, strength, and endurance. We aimed to characterize the genomic response of the participants' vastus lateralis (VL) on day 64 of bed rest with and without exercise countermeasures. METHODS: Twenty-two healthy young males were randomized into three groups: 1) bed rest only (n = 7), 2) bed rest + aerobic (6 d/wk) and resistance training (3 d/wk) on standard equipment (n = 7), and 3) bed rest + aerobic and resistance training using a flywheel device (n = 8). The VL gene and microRNA microarrays were analyzed using GeneSpring GX 14.9.1. RESULTS: Bed rest significantly altered the expression of 2113 annotated genes in at least one out of the three study groups (fold change (FC) > 1.2; P < 0.05). Interaction analysis revealed that exercise attenuated the bed rest effect of 511 annotated genes (FC 1.2, P < 0.05). In the bed rest only group, a predominant downregulation of genes was observed while in the two exercise groups there was a notable attenuation or reversal of this effect, with no significant differences between the two exercise modalities. Enrichment analysis identified functional categories and gene pathways, many of them related to the mitochondria. Additionally, bed rest significantly altered the expression of 35 microRNAs (FC > 1.2, P < 0.05) with no difference between the three groups. Twelve are known to regulate some of the mitochondrial-related genes that were altered following bed rest. CONCLUSIONS: Mitochondrial gene expression was a significant component of the molecular response to long-term bed rest. While exercise attenuated the FC in the downregulation of many genes, it did not completely counteract all the molecular consequences.

Exercise is also medicine for iron homeostasis.

High-intensity interval training (HIIT) is gaining popularity as an effective exercise modality to improve cardiometabolic health. Combining high-throughput/sensitivity proteome analyses in subcutaneous adipose tissue with biochemical blood measures, Larsen et al. recently provided mechanistic insights into a potential beneficial role of this exercise modality on iron homeostasis at the whole-body level.

Resting heart rate but not heart rate variability is associated with the normal-weight obesity phenotype.

OBJECTIVE: To determine differences in resting heart rate variability (HRV) and heart rate (HR) between young adults with normal-weight obesity (NWO) and normal-weight lean (NWL). METHODS: A total of 65 normal-weight individuals (18-25 years old, 50 women, body mass index 18.5 to 24.9 kg/m2 ) were included in this cross-sectional study. Body fat percentage was determined using a whole-body dual energy x-ray absorptiometry scanner. Resting HRV and HR were assessed with the Polar RS800CX. Forty-one participants were classified as NWO and 24 NWL using cutoff points for body fat percentage (33.3% for women and 23.1% for men). RESULTS: There were no differences in HRV between NWO and NWL groups (all p > .05). HR was higher in NWO (mean 70 beats per minute [bpm], standard deviation [SD] 8) than in NWL adults (mean 65 bpm, SD 10), the adjusted mean difference 5 bpm (95% CI, 0 to 10 bpm). CONCLUSION: HR is a noninvasive biomarker and relatively cheap, fast, and easy to measure that could detect "apparently healthy" young individuals with an adverse cardiovascular disease risk profile despite presenting a normal body weight.

Exercise-induced changes in plasma S-Klotho levels are associated with the obtained enhancements of heart rate variability in sedentary middle-aged adults: the FIT-AGEING study.

The shed form of the Klotho protein (S-Klotho) is considered a biomarker of longevity, but it is still unknown whether the levels are related to heart rate (HR) and heart rate variability (HRV); both of them greatly influenced by the ageing process, physical fitness, exercise, and health status. This study aimed (i) to investigate the association between S-Klotho plasma levels with HR and HRV parameters and (ii) to examine the association of exercise-induced changes in S-Klotho and those obtained in HR and HRV parameters after a 12-week exercise intervention in sedentary middle-aged adults. Sixty-six sedentary middle-aged adults participated in this study (50% women; 45-65 years old). Participants were randomized into 4 groups: (a) a control group (no exercise), (b) a physical activity recommendation from the World Health Organization group, (c) a high-intensity interval training group, and (d) a high-intensity interval training group adding whole-body electromyostimulation. S-Klotho plasma levels, HR, and HRV parameters (SDNN, RMSSD, high frequency, stress score, and sympathetic/parasympathetic ratio) were measured. At baseline, S-Klotho plasma levels were not related to HR and HRV parameters. After the intervention, exercise-induced changes in S-Klotho plasma levels were positively associated with changes in SDNN (ß=0.261; R2=0.102; p=0.014) and negatively related to changes in stress score and sympathetic/parasympathetic ratio (all ß=-0.257; R2 ranges between 0.092 and 0.131; all p<0.020). Our study suggests that higher S-Klotho plasma levels are related to increased vagal influence and reduced sympathetic tone in the autonomic nervous system in sedentary middle-aged adults after different training programs. ClinicalTrials.gov identifier: CT03334357.

Which indices of cardiorespiratory fitness are more strongly associated with brain health in children with overweight/obesity?

PURPOSE: To compare the strength of associations between different indices of cardiorespiratory fitness (CRF) and brain health outcomes in children with overweight/obesity. METHODS: Participants were 100 children aged 8-11 years. CRF was assessed using treadmill exercise test (peak oxygen uptake [V̇O2peak ], treadmill time, and V̇O2 at ventilatory threshold) and 20-metre shuttle run test (20mSRT, laps, running speed, estimated V̇O2peak using the equations by Léger et al., Mahar et al., and Matsuzaka et al.). Intelligence, executive functions, and academic performance were assessed using validated methods. Total gray matter and hippocampal volumes were assessed using structural MRI. RESULTS: V̇O2peak /body mass (ß = 0.18, 95% CI = 0.01-0.35) and treadmill time (ß = 0.18-0.21, 95% CI = 0.01-0.39) were positively associated with gray matter volume. 20mSRT laps were positively associated with executive functions (ß = 0.255, 95% CI = 0.089-0.421) and academic performance (ß = 0.199-0.255, 95% CI = 0.006-0.421), and the running speed was positively associated with executive functions (ß = 0.203, 95% CI = 0.039-0.367). Estimated V̇O2peak/Léger et al. was positively associated with intelligence, executive functions, academic performance, and gray matter volume (ß = 0.205-0.282, 95% CI = 0.013-0.500). Estimated V̇O2peak/Mahar et al. and V̇O2peak/Matsuzaka et al. (speed) were positively associated with executive functions (ß = 0.204-0.256, 95% CI = 0.031-0.436). CONCLUSION: Although V̇O2peak is considered the gold standard indicator of CRF in children, peak performance (laps or running speed) and estimated V̇O2peak/Léger et al. derived from 20mSRT had stronger and more consistent associations with brain health outcomes than other indices of CRF in children with overweight/obesity.

Effects of exercise on whole-blood transcriptome profile in children with overweight/obesity.

BACKGROUND: The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in childhood. We set out to investigate the effects of a 20-week exercise intervention on whole-blood transcriptome profile (RNA-seq) in children with overweight/obesity. METHODS: Twenty-four children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20-week exercise program (intervention group; n = 10), or to a no-exercise control group (n = 14). Whole-blood transcriptome profile was analyzed using RNA-seq by STRT technique with GlobinLock technology. RESULTS: Following the 20-week exercise intervention program, 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p-value <0.05), while after multiple correction, no significant difference between exercise and control groups persisted in gene expression profiles (FDR >0.05). Genes enriched in GO processes and molecular pathways showed different immune response in boys (antigen processing and presentation, infections, and T cell receptor complex) and in girls (Fc epsilon RI signaling pathway) (FDR <0.05). CONCLUSION: These results suggest that 20-week exercise intervention program alters the molecular pathways involved in immune processes in children with overweight/obesity.

Intra-Assessment Resting Metabolic Rate Variability Is Associated with Cardiometabolic Risk Factors in Middle-Aged Adults.

The intra-assessment resting metabolic rate variability is related to cardiometabolic health, as suggested by previous literature. We studied whether that variability (expressed as coefficient of variation [CV; %]) for oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and resting energy expenditure (REE) is similar between men and women, and if is similarly associated with cardiometabolic risk factors. Gas exchange in 72 middle-aged adults was measured by indirect calorimetry. Anthropometrics and body composition, cardiorespiratory fitness, circulating cardiometabolic risk factors, and heart rhythm parameters were also determined. Men and women presented similar intra-assessment resting metabolic rate variability (all p > 0.05). Notably, in men, CV for RER was positively associated with BMI and adiposity (both standardized ß = 0.35, Ps ≤ 0.048), while CVs for VO2, VCO2, and REE were negatively associated (standardized ß ranged from -0.37 to -0.46, all p ≤ 0.036) with cardiometabolic risk factors. In women, CVs for VCO2 and REE were negatively associated with adiposity (both standardized ß = -0.36, Ps ≤ 0.041) and cardiometabolic risk Z-score (standardized ß = -0.40 and -0.38, respectively, Ps ≤ 0.05). In conclusion, intra-assessment resting metabolic rate variability could be considered an indicator of cardiometabolic health in middle-aged adults.

Resting Metabolic Rate of Individuals.

The resting metabolic rate (RMR) represents the energy required to sustain normal body functions and homeostasis in an awake individual under ambient thermoneutral conditions and during rest [...].

Gene-exercise interaction on brain health in children with overweight/obesity: the ActiveBrains randomized controlled trial.

We investigated the interaction between a genetic score and an exercise intervention on brain health in children with overweight/obesity. One hundred one children with overweight/obesity (10.0 ± 1.5 yr, 59% girls) were randomized into a 20-wk combined exercise intervention or a control group. Several cognitive and academic outcomes were measured with validated tests. Hippocampal volume was quantified using magnetic resonance imaging. Six brain health-related polymorphisms [rs6265 (BDNF), rs2253206 (CREB1), rs2289656 (NTRK2), rs4680 (COMT), rs429358, and rs7412 (APOE)] were genotyped. Cognitive flexibility and academic skills improved significantly more in the exercise than in the control group only in the children with a "favorable" genetic profile [mean z-score, 0.41-0.67 (95% CI 0.11 to 1.18)], yet not in those with "less favorable" genetic profile. An individual response analysis showed that children responded to exercise in cognitive flexibility only in the "genetically favorable" group [i.e., 62% of them had a meaningful (≥0.2 Cohen d) increase in the exercise group compared with only 25% in the control group]. This finding was consistent in per-protocol and intention-to-treat analyses (P = 0.01 and P = 0.03, respectively). The results were not significant or not consistent for the rest of outcomes studied. Our findings suggest that having a more favorable genetic profile makes children with overweight/obesity more responsive to exercise, particularly for cognitive flexibility.NEW & NOTEWORTHY Interindividual differences have been reported in brain health-related outcomes in response to exercise interventions in adults, which could be partially explained by genetic background differences. However, the role of genetic polymorphisms on brain health-related outcomes in response to exercise interventions remains unexplored in pediatric population. The current study in children with overweight/obesity showed that a genetic score composed of six brain health-related polymorphisms (BDNF, CREB1, NTRK2, COMT, and APOE) regulated the exercise-induced response on several brain health outcomes, yet mainly and more consistently on cognitive flexibility.

Shared gene expression signatures between visceral adipose and skeletal muscle tissues are associated with cardiometabolic traits in children with obesity.

Obesity in children is related to the development of cardiometabolic complications later in life, where molecular changes of visceral adipose tissue (VAT) and skeletal muscle tissue (SMT) have been proven to be fundamental. The aim of this study is to unveil the gene expression architecture of both tissues in a cohort of Spanish boys with obesity, using a clustering method known as weighted gene co-expression network analysis. For this purpose, we have followed a multi-objective analytic pipeline consisting of three main approaches; identification of gene co-expression clusters associated with childhood obesity, individually in VAT and SMT (intra-tissue, approach I); identification of gene co-expression clusters associated with obesity-metabolic alterations, individually in VAT and SMT (intra-tissue, approach II); and identification of gene co-expression clusters associated with obesity-metabolic alterations simultaneously in VAT and SMT (inter-tissue, approach III). In both tissues, we identified independent and inter-tissue gene co-expression signatures associated with obesity and cardiovascular risk, some of which exceeded multiple-test correction filters. In these signatures, we could identify some central hub genes (e.g., NDUFB8, GUCY1B1, KCNMA1, NPR2, PPP3CC) participating in relevant metabolic pathways exceeding multiple-testing correction filters. We identified the central hub genes PIK3R2, PPP3C and PTPN5 associated with MAPK signaling and insulin resistance terms. This is the first time that these genes have been associated with childhood obesity in both tissues. Therefore, they could be potential novel molecular targets for drugs and health interventions, opening new lines of research on the personalized care in this pathology. This work generates interesting hypotheses about the transcriptomics alterations underlying metabolic health alterations in obesity in the pediatric population.

Effects of an Exercise Program on Cardiometabolic and Mental Health in Children With Overweight or Obesity: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Childhood obesity is a risk factor associated with type 2 diabetes, cardiovascular disease, and mental disorders later in life. Investigation of the parallel effects of a defined exercise program on cardiometabolic and mental health in children with overweight or obesity may provide new insights on the potential benefits of exercise on overall health. Objective: To investigate the effects of a 20-week exercise program on cardiometabolic and mental health in children with overweight or obesity. Design, Setting, and Participants: This secondary analysis of a parallel-group randomized clinical trial was conducted in Granada, Spain, from November 1, 2014, to June 30, 2016. Data analyses were performed between February 1, 2020, and July 14, 2022. Children with overweight or obesity aged 8 to 11 years were eligible, and the study was performed in an out-of-school context. Intervention: The exercise program included 3 to 5 sessions/wk (90 min/session) of aerobic plus resistance training for 20 weeks. The wait-list control group continued with their usual routines. Main Outcomes and Measures: Cardiometabolic outcomes as specified in the trial protocol included body composition (fat mass, fat-free mass, and visceral adipose tissue), physical fitness (cardiorespiratory, speed-agility, and muscular), and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure). Cardiometabolic risk score (z score) was calculated based on age and sex reference values for levels of triglycerides, inverted high-density lipoprotein cholesterol, and glucose, the mean of systolic and diastolic blood pressure, and waist circumference. An additional cardiometabolic risk score also included cardiorespiratory fitness. Mental health outcomes included an array of psychological well-being and ill-being indicators. Results: The 92 participants included in the per-protocol analyses (36 girls [39%] and 56 boys [61%]) had a mean (SD) age of 10.0 (1.1) years. The exercise program reduced the cardiometabolic risk score by approximately 0.38 (95% CI, -0.74 to -0.02) SDs; decreased low-density lipoprotein cholesterol level by -7.00 (95% CI, -14.27 to 0.37) mg/dL (to convert to mmol/L, multiply by 0.0259), body mass index (calculated as weight in kilograms divided by height in meters squared) by -0.59 (95% CI, -1.06 to -0.12), fat mass index by -0.67 (95% CI, -1.01 to -0.33), and visceral adipose tissue by -31.44 (95% CI, -58.99 to -3.90) g; and improved cardiorespiratory fitness by 2.75 (95% CI, 0.22-5.28) laps in the exercise group compared with the control group. No effects were observed on mental health outcomes. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, an aerobic plus resistance exercise program improved cardiometabolic health in children with overweight or obesity but had no effect on mental health. Trial Registration: ClinicalTrials.gov Identifier: NCT02295072.

A bout of endurance and resistance exercise transiently decreases plasma levels of bile acids in young, sedentary adults.

Circulating bile acids (BA) are signaling molecules that control glucose and lipid metabolism. However, the effects of acute exercise on plasma levels of BA in humans remain poorly understood. Here, we evaluate the effects of a bout of maximal endurance exercise (EE) and resistance exercise (RE) on plasma levels of BA in young, sedentary adults. Concentration of eight plasma BA was measured by liquid chromatography-tandem mass spectrometry before and 3, 30, 60, and 120 min after each exercise bout. Cardiorespiratory fitness (CRF) was assessed in 14 young adults (21.8 ± 2.5 yo, 12 women); muscle strength was assessed in 17 young adults (22.4 ± 2.5 yo, 11 women). EE transiently decreased plasma levels of total, primary, and secondary BA at 3 and 30 min after exercise. RE exerted a prolonged reduction in plasma levels of secondary BA (p < 0.001) that lasted until 120 min. Primary BA levels of cholic acid (CA) and chenodeoxycholic acid (CDCA) were different across individuals with low/high CRF levels after EE (p ≤ 0.044); CA levels were different across individuals with low/high handgrip strength levels. High CRF individuals presented higher levels of CA and CDCA 120 min after exercise vs baseline (+77% and +65%) vs the low CRF group (-5% and -39%). High handgrip strength levels individuals presented higher levels of CA 120 min after exercise versus baseline (+63%) versus the low handgrip strength group (+6%). The study findings indicate that an individual's level of physical fitness can influence how circulating BA respond to both endurance and resistance exercise. Additionally, the study suggests that changes in plasma BA levels after exercising could be related to the control of glucose homeostasis in humans.

Fit-Fat Index is better associated with heart rate variability compared to fitness and fatness alone as indicators of cardiometabolic human health.

OBJECTIVES: Cardiorespiratory fitness and fatness indicators have been related to heart rate variability (HRV) parameters. The Fit-Fat Index (FFI) is a single index combining cardiorespiratory fitness and fatness indicators. To the best of our knowledge, no studies have previously analyzed whether FFI are related to cardiac autonomic nervous system activity assessed through HRV parameters. This study aimed (i) to examine the association of cardiorespiratory fitness, fatness indicators, and FFI with HRV parameters; and (ii) to report what of the different fatness indicators included in FFI is better associated with HRV parameters in sedentary adults. METHODS: One hundred and fifty healthy adults (74 women; 76 men), aged between 18 and 65 years old, participated in this cross-sectional study. We measured cardiorespiratory fitness (maximal oxygen consumption) and fatness indicators (waist-to-height ratio [WHR], fat mass percentage [FM%] and visceral adipose tissue [VAT]). Three FFIs were calculated as the quotient between cardiorespiratory fitness and one out of three possible fatness indicators: Fit-Fat Index calculated waist-to-height ratio (FFIWHR ), Fit-Fat Index calculated with FM% (FFIFM% ), and Fit-Fat Index calculated with VAT (FFIVAT ). HRV parameters were measured in resting conditions using a Polar RS800CX. RESULTS: FFIWTHR , FFIFM% and FFIVAT were related to different HRV parameters (ß ranges between -0.507 and 0.529; R2 ranges between 0.096 and 0.275; all p < .001) and the association was stronger with HRV parameters than the isolated fitness or fatness indicators (ß ranges between -0.483 and 0.518; R2 ranges between 0.071 and 0.263; all p < .001). FFIVAT was the index more consistently associated with HRV parameters (ß ranges between -0.507 and 0.529; R2 ranges between 0.235 and 0.275; all p < .001). CONCLUSION: Our study suggests that compound FFIs are better predictors of HRV parameters than either cardiorespiratory fitness or fatness indicators alone. The FFIVAT was the best index in terms of its association to HRV.

Association of muscular strength and targeted proteomics involved in brain health in children with overweight/obesity.

Muscular strength has been positively associated with better brain health indicators during childhood obesity. However, the molecular mechanisms underlying the positive impact of muscular strength in brain health are poorly understood. We aimed to study the association of muscular strength with neurology-related circulating proteins in plasma in children with overweight/obesity and to explore the role of cardiorespiratory fitness (CRF) as a confounder. The participants were 86 Caucasian children (10.1 ± 1.1 years old; 41% girls) from the ActiveBrains project. Muscular strength was measured by field and laboratory tests. CRF was assessed with an incremental treadmill test. Olink's technology was used to quantify 92 neurology-related proteins in plasma. Protein-protein interactions were computed using the STRING website. Muscular strength was positively associated with 12 proteins (BetaNGF, CDH6, CLEC10A, CLM1, FcRL2, HAGH, IL12, LAIR2, MSR1, SCARB2, SMOC2, and TNFRSF12A), and negatively associated with 12 proteins (CLEC1B, CTSC, CTSS, gal-8, GCP5, NAAA, NrCAM, NTRK2, PLXNB3, RSPO1, sFRP3, and THY1). After adjustment for CRF, muscular strength was positively associated with eight proteins (BetaNGF, CDH6, CLEC10A, FcRL2, LAIR2, MSR1, SCARB2, and TNFRSF12A) and negatively associated with two proteins (gal-8 and NrCAM). After applying FDR correction, only CLEC10A remained statistically significant. In conclusion, muscular strength was associated with blood circulating proteins involved in several biological processes, particularly anti-inflammatory response, lipid metabolism, beta amyloid clearance, and neuronal action potential propagation. More powered studies are warranted in pediatric populations to contrast or confirm our findings.

Heart Rate Variability and Cardiorespiratory Fitness in Youth Populations: The Impact of Heart Rate on Data Analysis.

The positive association between heart rate variability and cardiorespiratory fitness in youth populations is unclear. In this regard, several methodological aspects related to heart rate variability analysis could partially explain the disagreement between studies. To the best of the authors' knowledge, the influence of the heart rate on data analysis is unclear. In the present short communication, we discuss the impact of the heart rate on the associations between heart rate variability and cardiorespiratory fitness in youth. In addition, we proposed some aspects that should be considered for statistical analyses when the relationship between heart rate variability and cardiorespiratory fitness is studied. Finally, we should acknowledge that these recommendations may be applicable for other health-related outcomes different than cardiorespiratory fitness (e.g., inflammatory markers, cognition, cardiovascular disease status).

Detraining Effect on Cardiac Autonomic Response to an All-Out Sprint Exercise in Trained Adolescent Swimmers.

PURPOSE: This study aimed to investigate the effects of a 5-week training cessation on the cardiac autonomic response after a 50-m swimming time-trial test. METHODS: Twenty trained and highly trained adolescent swimmers (17.1 [2.7] y) performed a 50-m front-crawl all-out test before (visit 1) and after a 5-week training cessation (visit 2). After the warm-up, heart-rate variability (HRV) was recorded in a seated position using a Polar RS800CX heart-rate monitor during the 10 minutes before (preexercise) and immediately after the 50-m front-crawl all-out test (postexercise). Two-way analysis of variance (time × visit) and analysis of covariance were conducted to compute the effect of the 50-m all-out test on vagal-related HRV parameters (mean R-R, standard deviation of R-R intervals [SDNN], square root of the mean squared differences between successive R-R intervals [RMSSD], the percentage number of pairs of adjacent normal R-R intervals differing by more than 50 milliseconds in the entire recording [pNN50], and power in the high frequency [HF]) with Bonferroni post hoc test. RESULTS: All the HRV parameters had a time main effect (P < .05), showing a reduction after the 50 m in both visits (P < .05). All the variables exhibited a visit main effect (P < .05); the preexercise and postexercise mean R-R, natural logarithm SDNN, natural logarithm RMSSD, and natural logarithm HF values declined after the training cessation (P < .05). Natural logarithm pNN50 preexercise values were reduced in visit 2 compared with visit 1 (P < .05). Only mean R-R was further reduced in response to the test in visit 2 compared with visit 1 (P < .05). CONCLUSIONS: After 5 weeks of training cessation, all the preexercise and postexercise vagal-related HRV parameters evidenced a reduction, suggesting an impairment in swimmers' physical status. Coaches should be cautious with training loads at the start of the season.

Cardiorespiratory fitness and targeted proteomics involved in brain and cardiovascular health in children with overweight/obesity.

Cardiorespiratory fitness (CRF) is inversely associated with cardiovascular disease (CVD) risk factors and brain health impairments. However, the molecular mechanisms linking CRF to health in children are poorly understood. We aimed to examine protein levels related to brain health and CVD in plasma of fit compared to unfit children with overweight/obesity (OW/OB). Eighty-seven children with OW/OB (10.08 ± 1.1 years, 59% boys) from the ActiveBrains project were included. CRF was measured by performing a treadmill test, and children were categorized into fit or unfit. Targeted proteomics in plasma was performed using Olink's proximity extension assay technology of Neurology panel in the whole sample and of Cardiovascular panel in a subsample. Sixteen proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) were differentially expressed between fit and unfit children with OW/OB after adjusting for sex, maturational status, and body mass index. However, statistically significant differences disappeared after applying FDR correction. Potential candidate proteins related to CRF levels in children with OW/OB were detected, being involved in several biological processes such as neurogenesis, immune/inflammatory response, signal transduction, platelet activation. Nevertheless, these preliminary findings should be confirmed or contrasted in future studies using larger sample sizes, longitudinal and experimental designs.HighlightsThe molecular mechanisms underlying the link of cardiorespiratory fitness (CRF) with cardiovascular and brain health in children with overweight/obesity (OW/OB) are poorly understood.Targeted proteomic analysis revealed differentially expressed proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) in plasma of "Fit" compared to "Unfit" children with OW/OB. These proteins are involved in several biological processes such as immune/inflammatory response, neurogenesis, signal transduction, and cellular metabolic process.Longitudinal and experimental studies are warranted to reveal how improvements in CRF are related to changes in circulating levels of the abovementioned proteins and how they might reduce cardiovascular diseases risk factors and brain health impairments later in life.