Exercise and tumor proteome: Insights from a neuroblastoma model.

BACKGROUND/AIM: The impact of exercise on pediatric tumor biology is essentially unknown. We investigated the effects of regular exercise on tumor proteome profile (as assessed with liquid chromatography with tandem mass spectrometry) in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma (HR-NB). METHODS: Tumor samples of 14 male mice (aged 6-8 weeks) that were randomly allocated into an exercise (5-week combined aerobic and resistance training) or nonexercise control group (6 and 8 mice per group, respectively) were analyzed. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network and enrichment analyses. The Systems Biology Triangle (SBT) algorithm was applied for analyses at the functional category level. RESULTS: Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, compared to controls [false discovery rate (FDR)<0.05], which were enriched in metabolic pathways, aminoacid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling pathway (FDR<0.05). The SBT algorithm indicated that 184 and 126 categories showed a lower and higher abundance, respectively, in the tumors of exercised mice (FDR<0.01). Categories with lower abundance were involved in energy production while those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression. CONCLUSION: Regular exercise altered the abundance of hundreds of intratumoral proteins and molecular pathways, particularly those involved in energy metabolism, apoptosis, and tumor suppression. These findings provide preliminary evidence of the molecular mechanisms underlying potential effects of exercise in HR-NB.

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.

Heart Rate and Its Variability Are Associated With Resting Metabolic Rate and Substrate Oxidation in Young Women but Not in Men.

BACKGROUND: This study aims to examine the relationship between resting vagal-related heart rate variability (HRV) parameters and heart rate (HR) with resting metabolic rate (RMR) and respiratory exchange ratio (RER) in young adults. METHODS: A total of 74 young adults (22 ± 2 years old, 51 women) were included in this cross-sectional study. HRV was assessed using a HR monitor, whereas RMR and RER were determined by indirect calorimetry. RESULTS: Linear regression analyses showed a positive association between HR and RER in women (standardized ß = 0.384, p = 0.008), while negative associations were observed between vagal-related HRV parameters and RER in women (ß ranged from -0.262 to -0.254, all p ≤ 0.042). No significant association was found between the abovementioned physiological parameters in men. CONCLUSION: Here, we show that HR is positively associated with RER in young women but not in men, while vagal-related HRV parameters are inversely related to RMR, therefore suggesting a potential sexual dimorphism between cardiac rhythm and its relationship with markers of cardiometabolic health status. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02365129.

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.

Targeted proteomics involved in cardiovascular health and heart rate variability in children with overweight/obesity.

BACKGROUND: Children with overweight/obesity often exhibit alterations in their plasma protein profiles and reduced heart rate variability (HRV). Plasma proteomics is at the forefront of identifying biomarkers for various clinical conditions. We aimed to examine the association between plasma-targeted proteomics involved in cardiovascular health and resting vagal-related HRV parameters in children with overweight/obesity. METHODS: Forty-four children with overweight/obesity (10.2 ± 1.1 years old; 52% boys) participated in the study. Olink's technology was used to quantify 92 proteins involved in cardiovascular health. HRV was measured using a heart rate monitor (Polar RS800CX). Four resting vagal-related HRV parameters were derived in time- and frequency-domain. RESULTS: Eight proteins (KIM1, IgG Fc receptor II-b, IDUA, BOC, IL1RL2, TNFRSF11A, VSIG2, and TF) were associated with at least one out of the four vagal-related HRV parameters (ß values ranging from -0.188 to 0.288; all p < .05), while KIM1, IDUA, and BOC associated with ≥ three vagal-related HRV parameters. Multiple hypothesis testing corrections did not reach statistical significance (false discovery rate [FDR >0.05]). CONCLUSION: Plasma-targeted proteomics suggested novel biomarkers for resting vagal-related HRV parameters in children with overweight/obesity. Future studies using larger cohorts and longitudinal designs should confirm our findings and their potential clinical implications.

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.

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.

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.

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.

Associations between heart rate variability and maximal fat oxidation in two different cohorts of healthy sedentary adults.

BACKGROUND AND AIMS: Resting heart rate variability (HRV) and maximal fat oxidation (MFO) during exercise are both considered as a noninvasive biomarkers for early detection of cardiovascular risk factors. Thus, this study aimed to analyze the relationship between resting HRV parameters and MFO during exercise, and the intensity of exercise that elicit MFO (Fatmax) in healthy sedentary adults. METHODS AND RESULTS: A total of 103 healthy young adults (22.2 ± 2.3 years old, 67% female; from the ACTIBATE cohort) and 67 healthy middle-aged adults (53.1 ± 5.0 years old, 52% female; from the FIT-AGEING cohort) were included in this cross-sectional study. HRV was assessed using a Polar RS800CX heart rate monitor, while MFO and Fatmax were determined during a graded exercise treadmill test using indirect calorimetry. No significant associations were observed for healthy young adults (standardized ß coefficients ranged from -0.063 to 0.094, and all P ≥ 0.347) and for middle-aged adults (standardized ß coefficients ranged from -0.234 to 0.090, and all P ≥ 0.056). Nevertheless, only a weak association was observed between one HRV parameter in time-domain (the percentage of R-R intervals that shows a difference higher than 50 ms [pNN50]) and MFO in the cohort of middle-aged adults (ß coefficient = -0.279, and P = 0.033). CONCLUSION: The results of this study suggest that resting HRV parameters are not associated with MFO and Fatmax during exercise in two independent cohorts of healthy sedentary young and middle-aged adults, respectively.

Associations between different heart rate variability ratios and cardiometabolic risk factors in young adults.

AIMS: To study the association of two different heart rate variability (HRV) ratios with cardiovascular disease (CVD) risk factors in young adults. METHOD: A total of 132 participants (89 women) were included in this cross-sectional study. We assessed their HRV and computed the low frequency-to-high frequency ratio (LF/HF) and, from the Poincaré plot, the ratio of the inverse of the longitudinal (SD2) to the transversal (SD1) axes ([1000/SD2]/SD1; sympathetic: parasympathetic [S:PS] ratio). From blood samples, we determined total cholesterol, high-density (HDL-C) and low-density lipoprotein-cholesterol, triglycerides, glucose, insulin, and the homeostatic model assessment of insulin resistance (HOMA) index. Multiple linear regression models were adjusted for age. RESULTS: Both, the LF/HF and the S:PS ratios, were positively associated with glucose metabolism markers (glucose, insulin, HOMA index), and negatively associated with HDL-C in women but not in men. CONCLUSION: We showed that the LF/HF and the S:PS are associated similarly with CVD risk factors in young women.

Different exercise training modalities similarly improve heart rate variability in sedentary middle-aged adults: the FIT-AGEING randomized controlled trial.

PURPOSE: This study aimed to investigate the influence of different exercise training modalities on heart rate variability (HRV) in sedentary middle-aged adults; and to study whether changes in health-related outcomes (i.e., body composition and cardiometabolic risk) are associated with those hypothetical HRV changes in sedentary middle-aged adults. METHODS: A total of 66 middle-aged adults (53.6 ± 4.4 years old; 50% women) were enrolled in the FIT-AGEING study. We conducted a 12-week randomized controlled trial. The participants were randomly assigned to 4 groups: (a) a control group (no exercise); (b) a physical activity recommendation from the World Health Organization group (PAR); (c) a high-intensity interval training group (HIIT); and (d) a high-intensity interval training group adding whole-body electromyostimulation (HIIT + EMS). RESULTS: All exercise training modalities induced changes in HRV parameters (all P ≤ 0.001) without statistical differences between them (all P > 0.05). We found associations between changes in body composition and cardiometabolic risk and exercise-related changes in HRV. CONCLUSION: Our results suggest that different exercise interventions (i.e., PAR, HIIT and HIIT + EMS) induced an enhancement of HRV in sedentary middle-aged adults. Our findings support the notion that exercise-related changes in HRV are associated with changes in body composition and cardiometabolic risk after the intervention program CLINICAL TRIAL REGISTRY: NCT03334357 (ClinicalTrials.gov). November 7, 2017 retrospectively registered.

Leptin levels were negatively associated with lumbar spine bone mineral content in children with overweight or obesity.

AIM: Adipokines seem to play a role in bone morphogenesis, although this also depends on the mechanical forces applied to the skeleton. The aim was to assess the relationships of resting leptin and adiponectin with bone parameters and whether high muscular fitness levels affect these relationships in children with overweight or obesity. METHODS: This cross-sectional study took part from 2014 to 2016 in Granada, Spain. Participants were recruited from University Hospitals, and we also used advertisements in local media and school contacts in the city. Adipokines were analysed in plasma. Muscular fitness was assessed by one repetition maximum in bench and leg press tests. Dual-energy X-ray absorptiometry was used to measure bone parameters. RESULTS: We included 84 children (10.0 ± 1.2y; 63% boys) in this analysis. Leptin was negatively associated with lumbar spine bone mineral content (ß = -0.162, p = 0.053). No significant interaction was found for muscular fitness. Simple slope estimates suggested that children performing more than 133.3 kg in leg press test ameliorated the negative association between leptin and lumbar spine bone mineral content. CONCLUSION: Leptin levels were negatively associated with lumbar spine bone mineral content in children with overweight or obesity. A high muscular fitness at the lower body could counteract this association.

Distinct whole-blood transcriptome profile of children with metabolic healthy overweight/obesity compared to metabolic unhealthy overweight/obesity.

BACKGROUND: Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes. The underlying mechanisms for those differences are still unclear. This study aimed to analyze the whole-blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes. METHODS: Twenty-seven children with OW/OB (10.1 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein-cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers were additionally determined. Total blood RNA was analyzed by 5'-end RNA-sequencing. RESULTS: Whole-blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. Thirty-two genes differentially expressed were linked to metabolism, mitochondrial, and immune functions. CONCLUSIONS: The identified gene expression patterns related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity. IMPACT: A distinct pattern of whole-blood transcriptome profile (RNA-seq) was identified in children with metabolic healthy overweight/obesity (MHO) compared to metabolic unhealthy overweight/obesity (MUO) phenotype. The most relevant genes in understanding the molecular basis underlying the MHO/MUO phenotypes in children could be: RREB1, FAM83E, SLC44A1, NRG1, TMC5, CYP3A5, TRIM11, and ADAMTSL2. The identified whole-blood transcriptome profile related to metabolism, mitochondrial, and immune functions contribute to a better understanding of why a subset of the population remains metabolically healthy despite having overweight/obesity.

Physical fitness and brain source localization during a working memory task in children with overweight/obesity: The ActiveBrains project.

The present study aims (i) to examine the association of physical fitness components (i.e., cardiorespiratory fitness, speed-agility, and muscular fitness) with brain current source density during working memory; and (ii) to examine whether fitness-related current density was associated to working memory performance and academic achievement. Eighty-five children with overweight/obesity aged 8-11 years participated in this cross-sectional study. Physical fitness components were assessed using the ALPHA test battery. Electroencephalography recordings were performed during a Delayed Non-Match-to-Sample task that assessed working memory. Brain source analysis was carried out using sLORETA to estimate regional current source density differences between high and low (H-L) working memory loads. Academic achievement was measured by the Spanish version of the Woodcock-Johnson III test battery. The main results showed that higher cardiorespiratory fitness was associated with higher H-L current density differences in frontal, limbic, and occipital regions during encoding and maintenance task's phases (ß≥0.412, p ≤ 0.019). A limbic area was further related to better working memory performance (ß=0.267, p = 0.005). During retrieval, higher cardiorespiratory fitness was also associated with higher current density in temporal regions (ß=0.265, p = 0.013), whereas lower muscular fitness was associated with higher current density in frontal regions (ß=-0.261, p = 0.016). Our results suggest that cardiorespiratory fitness, but not speed-agility nor muscular fitness, is positively associated with brain current source density during working memory processes in children with overweight/obesity. Fitness-related current density differences in limbic regions were associated with better working memory.

Cardiorespiratory fitness in children with overweight/obesity: Insights into the molecular mechanisms.

OBJECTIVES: High cardiorespiratory fitness (CRF) levels reduce the risk of developing cardiovascular disease (CVD) during adulthood. However, little is known about the molecular mechanisms underlying the health benefits of high CRF levels at the early stage of life. This study aimed to analyze the whole-blood transcriptome profile of fit children with overweight/obesity (OW/OB) compared to unfit children with OW/OB. DESIGN: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were evaluated. VO2 peak was assessed using a gas analyzer, and participants were categorized into fit or unfit according to the CVD risk-related cut-points. Whole-blood transcriptome profile (RNA sequencing) was analyzed. Differential gene expression analysis was performed using the limma R/Bioconductor software package (analyses adjusted by sex and maturational status), and pathways' enrichment analysis was performed with DAVID. In addition, in silico validation data mining was performed using the PHENOPEDIA database. RESULTS: 256 genes were differentially expressed in fit children with OW/OB compared to unfit children with OW/OB after adjusting by sex and maturational status (FDR < 0.05). Enriched pathway analysis identified gene pathways related to inflammation (eg, dopaminergic and GABAergic synapse pathways). Interestingly, in silico validation data mining detected a set of the differentially expressed genes to be related to CVD, metabolic syndrome, hypertension, inflammation, and asthma. CONCLUSION: The distinct pattern of whole-blood gene expression in fit children with OW/OB reveals genes and gene pathways that might play a role in reducing CVD risk factors later in life.

Inflammatory markers and bone mass in children with overweight/obesity: the role of muscular fitness.

OBJECTIVES: To examine which inflammatory markers are associated with bone mass and whether this association varies according to muscular fitness in children with overweight/obesity. METHODS: Plasma interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), epidermal growth factor, vascular endothelial growth factor A (VEGF), and C-reactive protein were analyzed in 55 children aged 8-11 years. A muscular fitness score was computed. Bone mineral content (BMC) of the total body-less head (TBLH) and lumbar spine (LS) were assessed using dual-energy x-ray absorptiometry. RESULTS: IL-6 (ß = -0.136) and VEGF (ß = -0.099) were associated with TBLH BMC, while TNF-α (ß = -0.345) and IL-1ß (ß = 0.212) were associated with LS BMC (P < 0.05). The interaction effect of muscular fitness showed a trend in the association of VEGF with TBLH BMC (P = 0.122) and TNF-α with LS BMC (P = 0.057). Stratified analyses by muscular fitness levels showed an inverse association of VEGF with TBLH BMC (ß = -0.152) and TNF-α with LS BMC (ß = -0.491) in the low-fitness group, while no association was found in the high-fitness group. CONCLUSION: IL-6, VEGF, TNF-α, and IL-1ß are significantly associated with bone mass. Higher muscular fitness may attenuate the adverse effect of high VEGF and TNF-α on bone mass.

Correction: Inflammatory markers and bone mass in children with overweight/obesity: the role of muscular fitness.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Effects of Exercise on Body Posture, Functional Movement, and Physical Fitness in Children With Overweight/Obesity.

Molina-Garcia, P, Mora-Gonzalez, J, Migueles, JH, Rodriguez-Ayllon, M, Esteban-Cornejo, I, Cadenas-Sanchez, C, Plaza-Florido, A, Gil-Cosano, JJ, Pelaez-Perez, MA, Garcia-Delgado, G, Vanrenterghem, J, and Ortega, FB. Effects of exercise on body posture, functional movement, and physical fitness in children with overweight/obesity. J Strength Cond Res 34(8): 2146-2155, 2020-This study aims to analyze whether a 13-week exercise program based on "movement quality" and "multi-games" can lead to simultaneous benefits to body posture, fundamental movements, and physical fitness of children with overweight/obesity. A total of 64 children (10.9 ± 1.3 years, 25.9 ± 3.8 kg·m, 38 girls and 26 boys) with overweight/obesity were assigned either to a 13-week exercise-based intervention group (IG) (n = 33) or to a control group (CG) (n = 31). Subjects underwent assessments of basic anthropometry (body mass and height), body posture (2-dimensional photogrammetry), fundamental movements (Functional Movement Screen), and physical fitness (1 repetition maximum [1RM] arm and leg press, and ALPHA test battery). After the exercise program, the IG reduced lower limb angle (high effect size: -0.82 SDs; p = 0.001) and plumb-tragus distance (low effect: -0.43 SDs; p = 0.002) in the sagittal plane and increased lower limb angle in the frontal plane (high effect: 0.82 SDs; p = 0.003) compared with the CG. The IG improved their performance in deep squat (p = 0.004), active straight leg raise (p < 0.001), 1RM arm (low effect: 0.46 SDs; p = 0.002), handgrip strength (medium effect: 0.53 SDs; p < 0.001), and standing long jump (medium effect: 0.59 SDs; p = 0.003), all compared with the CG. In conclusion, children with overweight/obesity who participated in our 13-week exercise program developed a better alignment of the head and lower limb, improved their performance in fundamental movements, and experienced global muscular strength gains compared with the peers who continued with their usual lives. Among other potential implications, these improvements could contribute to the prevention of musculoskeletal disorders associated with childhood obesity and could increase adherence by positioning these children in a better physical status to keep practicing exercise.