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Neurotrophic factors and cardiorespiratory fitness are both considered important in developmental trajectories but their link to brain health remains poorly understood. The aims of the study were to examine whether levels of plasma-derived neurotrophic factors were associated with brain health indicators in children with overweight or obesity; and to test whether these associations were moderated by cardiorespiratory fitness. 100 children (41% girls) were included in this analysis. Plasma levels of brain-derived neurotrophic factor, insulin-like growth factor-1, vascular endothelial growth factor A, and epidermal growth factor were determined by XMap technology. Academic performance and executive function were assessed using validated neuropsychological tests. Hippocampal volume was measured using magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20-m Shuttle Run Test. Insulin-like growth factor-1 was positively associated with cognitive flexibility. Stratified analyses by fitness categories (i.e. unfit vs. fit) showed that brain-derived neurotrophic factor was positively associated with right posterior hippocampal volume in fit children, and epidermal growth factor was negatively associated with right hippocampal, and right anterior hippocampal volumes in their unfit peers, with a moderating role of cardiorespiratory fitness in these associations. However, all these significant associations disappeared after correction for multiple comparisons. The association between neurotrophic factors and brain health indicators in children with overweight/obesity was neither strong nor consistent. These results could help enhance our understanding of determinants of brain health in children with overweight/obesity. Highlights This study provides novel findings on the associations between neurotrophic factors and a wide range of brain health indicators in children. This study additionally explored the role of cardiorespiratory fitness in these associations. The association between neurotrophic factors and brain health in children with overweight/obesity was neither strong nor consistent. Cardiorespiratory fitness moderated the associations of brain-derived neurotrophic factor and epidermal growth factor with right hippocampal volume.

ImportanceChildhood obesity is a risk factor for type 2 diabetes (T2D), cardiovascular disease, and mental disorders later in life. To investigate the parallel effects on cardiometabolic and mental health in children with overweight or obesity will provide new insights on the benefits of exercise on overall health.ObjectiveThis study aimed to investigate the effects of a 20-week exercise program on cardiometabolic and mental health in children with overweight or obesity.DesignParallel-group randomized clinical trial (RCT) conducted in Granada (Spain) from November 2014 to June 2016.SettingClinical setting.ParticipantsEligibility criteria included children with overweight or obesity aged 8 to 11.9 years from Granada (Spain) and surrounding areas.InterventionThe exercise program included 3-5 sessions/week (90 min/session) of aerobic plus resistance training for 20-weeks. The wait-list control group continued with their usual routines.Main Outcomes and MeasuresCardiometabolic outcomes 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 lipids biomarkers, glucose, insulin, and blood pressure). Cardiometabolic risk score (z-score) was calculated based on age and sex reference values for triglycerides, inverted high-density lipoprotein cholesterol, glucose, the average 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.ResultsThe ActiveBrains exercise program reduced the cardiometabolic risk score by ∼0.4 (95% confidence interval [CI95%]: −0.75, −0.03) standard deviations (SD). The exercise program had a positive effect on low-density lipoprotein cholesterol (−7.40 [CI95%: −14.82, 0.016] mg/dL), body mass index (−0.60 [CI95%: −1.07, −0.13] kg/m2), fat mass index (−0.70 [CI95%: −1.03 to −0.36] kg/m2), visceral adipose tissue (−34.05 [CI95%: −61.38, −6.73] g), and cardiorespiratory fitness (+3.07 [CI95%: 0.68, 5.45] laps) in the exercise group compared to controls. No effects were observed on mental health outcomes.Conclusions and RelevanceThe ActiveBrains exercise program improved cardiometabolic health in children with overweight or obesity, yet it had no effect on mental health. These findings support public health initiatives promoting exercise programs in children with excess body weight to prevent future cardiovascular comorbidities.Trial RegistrationClinicalTrials.gov Identifier: NCT02295072.Key PointsQuestionWhat are the parallel effects of exercise on cardiometabolic and mental health in children with excess of adiposity?FindingsIn this parallel-group randomized clinical trial of 109 children with overweight or obesity, a 20-week exercise program including aerobic plus resistance training improved body composition, cardiorespiratory fitness, and cardiometabolic risk factors. No effects on mental health were observed.MeaningExercise programs should be promoted in children with excess adiposity to improve their cardiometabolic health.

Background. Several non-persistent pesticides are endocrine disrupting chemicals and may impact on sexual maturation. Objective. To examine the association between urinary biomarkers of non-persistent pesticides and sexual maturation in adolescent males in the Environment and Childhood (INMA) Project. Methods. The metabolites of several pesticides were measured in spot urine samples collected from 201 boys aged 14–17 years, including: 3,5,6-trichloro-2-pyridinol (TCPy), metabolite of chlorpyrifos; 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), metabolite of diazinon; malathion diacid (MDA), metabolite of malathion; diethyl thiophosphate (DETP) and diethyl dithiophosphate, non-specific metabolites of organophosphates; 3-phenoxybenzoic acid (3-PBA) and dimethyl cyclopropane carboxylic acid, metabolites of pyrethroids; 1-naphthol (1-NPL), metabolite of carbaryl; and ethylene thiourea (ETU), metabolite of dithiocarbamate fungicides. Sexual maturation was assessed using Tanner stages, self-reported Pubertal Development Scale, and testicular volume (TV). Multivariate logistic regression was employed to examine associations between urinary pesticide metabolites and the odds of being in Tanner stage 5 of genital development (G5) or pubic hair growth (PH5); stage ≥4 of overall pubertal development, gonadarche, and adrenarche; or having mature TV (≥25 mL). Results. DETP concentrations>75th percentile (P75) were associated with lower odds of being in stage G5 (OR = 0.27; 95% CI = 0.10–0.70), detectable TCPy with lower odds of gonadal stage≥4 (OR = 0.50; 95% CI = 0.26–0.96), and intermediate detectable MDA concentrations (, CIBER Epidemiologia y Salud pública, Fondo de investigaciones sanitarias del Instituto Carlos III (código de expediente: PI17/01526), Fondo Europeo de Desarrollo Regional (FEDER) (código de expediente: CP16/00085)

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The aim of this study was to examine whether metabolically healthy overweight/obese children have greater global and regional gray matter volumes than their metabolically unhealthy peers. We further examined the association between gray matter volume and academic achievement, along with the role of cardiorespiratory fitness in these associations. A total of 97 overweight/obese children (10.0 &plusmn, 1.2 years) participated. We classified children as metabolically healthy/unhealthy based on metabolic syndrome cut-offs. Global and regional brain volumes were assessed by magnetic resonance imaging. Academic achievement was assessed using the Woodcock-Mu&ntilde, oz standardized test. Cardiorespiratory fitness was assessed by the 20 m shuttle run test. Metabolically healthy overweight/obese (MHO) children had greater regional gray matter volume compared to those who were metabolically unhealthy (MUO) (all p &le, 0.001). A similar trend was observed for global gray matter volume (p = 0.06). Global gray matter volume was positively related to academic achievement (&beta, = 0.237, p = 0.036). However, all the associations were attenuated or disappeared after adjusting for cardiorespiratory fitness (p &gt, 0.05). The findings of the present study support that metabolically healthy overweight/obese children have greater gray matter volume compared to those that are metabolically unhealthy, which is in turn related to better academic achievement. However, cardiorespiratory fitness seems to explain, at least partially, these findings.

The association between vitamin D [25(OH)D] and bone health has been widely studied in children. Given that 25(OH)D and bone health are associated with muscular fitness, this could be the cornerstone to understand this relationship. Hence, the purpose of this work was to examine if the relation between 25(OH)D and areal bone mineral density (aBMD) was mediated by muscular fitness in children with overweight/obesity. Eighty-one children (8-11 years, 53 boys) with overweight/obesity were included. Body composition was measured with dual energy X-ray Absorptiometry (DXA), 25(OH)D was measured in plasma samples and muscular fitness was assessed by handgrip and standing long jump tests (averaged z-scores were used to represent overall muscular fitness). Simple mediation analyses controlling for sex, years from peak height velocity, lean mass and season were carried out. Our results showed that muscular fitness z-score, handgrip strength and standing long jump acted as mediators in the relationship between 25(OH)D and aBMD outcomes (percentages of mediation ranged from 49.6% to 68.3%). In conclusion, muscular fitness mediates the association of 25(OH)D with aBMD in children with overweight/obesity. Therefore, 25(OH)D benefits to bone health could be dependent on muscular fitness in young ages., This study was supported by the Spanish Ministry of Economy and Competitiveness (Reference DEP2013-47540). This study takes place thanks to the additional funding from the University of Granada, UGR Research and Knowledge Transfer Fund (PPIT) 2016, Excellence actions: Units of Scientific Excellence; Scientific Unit of Excellence on Exercise and Health (UCEES) and the European Regional Development Funds (ERDF, ref. SOMM17/6107/UGR). In addition, this study was further supported by the SAMID III network, RETICS, funded by the PN I+D+I 2017-2021 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion and the European Regional Development Fund (ERDF) (Ref. RD16/0022). L.G-M is supported by a fellowship from “la Caixa” Foundation (ID 100010434) and the fellowship code is LCF/BQ/PR19/11700007. J.H.M. and J.M.-G. are supported by the Spanish Ministry of Education, Culture and Sport (FPU15/02645 and FPU14/06837, respectively).

Objective To examine the association between urinary metabolites of organophosphate (OP) pesticides and serum concentrations of thyroid and reproductive hormones in male adolescents and to assess the potential effect of interactions between OP pesticides and paraoxonase 1 (PON1) polymorphisms on hormone levels. Methods Study subjects (N = 117) were male 16- to 17-year-olds from the Environment and Childhood (INMA)-Granada cohort in Spain. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos/chlorpyrifos-methyl, 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), a metabolite of diazinon, and diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP), non-specific metabolites of OP pesticides, were measured in a spot urine sample from each subject and adjusted for creatinine. Levels of reproductive hormones (total testosterone [TT], estradiol [E2], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Mullerian hormone [AMH], insulin growth factor 1 [IGF-1], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), and PON1 Q192R and L55M polymorphisms were determined in blood drawn during the same clinical visit. Results Multiple linear regression models showed that detectable levels of TCPy were associated with an increase in DHEAS and decreases in E2, FSH, and AMH; detectable IMPy with increases in E2, DHEAS, FSH, AMH, and prolactin and decreases in SHBG and LH; and detectable DETP with marginally-significant increases in TT and TT3 and decreases in FSH, AMH, and prolactin. The effect of IMPy and DETP on DHEAS and TT levels, respectively, was higher in subjects that carried the PON1 55MM genotype, while the effect of TCPy, IMPy, and DETP on thyroid hormone levels was higher in PON1 192QR/RR or 55MM genotype carriers. Conclusions In male adolescents, non-occupational exposure to OP pesticides was associated with several changes in reproductive and thyroid hormone levels, and the magnitude of some associations was greater in adolescents genetically more susceptible to OP pesticide exposure who carry the PON1 55MM genotype.

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-1β (IL-1β), 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 (β = −0.136) and VEGF (β = −0.099) were associated with TBLH BMC, while TNF-α (β = −0.345) and IL-1β (β = 0.212) were associated with LS BMC (P

To examine which inflammatory markers are associated with bone mass and whether this association varies according to muscular fitness in children with overweight/obesity.Plasma interleukin-1β (IL-1β), 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.IL-6 (β = -0.136) and VEGF (β = -0.099) were associated with TBLH BMC, while TNF-α (β = -0.345) and IL-1β (β = 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 (β = -0.152) and TNF-α with LS BMC (β = -0.491) in the low-fitness group, while no association was found in the high-fitness group.IL-6, VEGF, TNF-α, and IL-1β are significantly associated with bone mass. Higher muscular fitness may attenuate the adverse effect of high VEGF and TNF-α on bone mass.

Objective To examine the association of urinary concentrations of arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), lead (Pb), manganese (Mn), and chromium (Cr) with blood pressure (BP) and serum hormone levels in male adolescents. Methods Participants were selected from the INMA (Environment and Childhood)-Granada cohort at their follow-up visit when aged 15–17 years. Metal concentrations were measured in urine samples using inductively coupled plasma mass spectrometry. Outcomes were BP measurements (systolic, diastolic, and pulse pressure) recorded during the visit and concurrent serum levels of thyroid hormones, sex hormones, and adrenal hormones. Associations were assessed by regression analysis in a sub-sample of 133 boys with available data on urinary metals, outcomes, and relevant covariates. Results Models simultaneously adjusted for all metals and other potential confounders showed that urinary As and Cd were both associated with slight elevations in systolic BP (0.70 mmHg, 95%CI = 0.11; 1.29 and 1.47, 95%CI = 0.30; 2.63, respectively, per each 50% increase in metal concentrations), and urinary As was also associated with an increased risk of elevated systolic BP (≥120 mmHg) (OR = 1.28, 95%CI = 1.04; 1.56). The presence of detectable levels of 4 and 5 versus 2–3 non-essential metals (As, Cd, Hg, Ni, Pb) per boy was associated with elevations in systolic BP of 5.84 mmHg (95%CI = 0.40; 11.3) and 7.01 mmHg (95%CI = 1.01; 13.0), respectively (p-trend = 0.05). Significant associations were also found between Hg and increased testosterone and luteinizing hormone (LH) and decreased thyroid-stimulating hormone (TSH); between the combination of As and Hg and increased LH and insulin-like growth factor 1; between Cr and decreased TSH; and between Cd and increased adrenocorticotropic hormone. Conclusions These findings suggest that combined exposure to toxic metals, especially As and Cd, may contribute to BP elevation in male adolescents and that exposure to Hg, As, Cd, and Cr may affect their hormone levels.

The new and recent advances in neuroelectric and neuroimaging technologies provide a new era for further exploring and understanding how brain and cognition function can be stimulated by environmental factors, such as exercise, and particularly to study whether physical exercise influences brain development in early ages. The present study, namely the ActiveBrains project, aims to examine the effects of a physical exercise programme on brain and cognition, as well as on selected physical and mental health outcomes in overweight/obese children. A total of 100 participants aged 8 to 11 years are randomized into an exercise group (N=50) or a control group (N=50). The intervention lasts 20-weeks, with 3-5 sessions per week of 90 min each, and is mainly focused on high-intensity aerobic exercise yet also includes muscle-strengthening exercises. The extent to what the intervention effect remains 8-months after the exercise programme finishes is also studied in a subsample. Brain structure and function and cognitive performance are assessed using structural and functional magnetic resonance imaging and electroencephalographic recordings. Secondary outcomes include physical health outcomes (e.g. physical fitness, body fatness, bone mass and lipid-metabolic factors) and mental health outcomes (e.g. chronic stress indicators and overall behavioural and personality measurements such as anxiety or depression). This project will substantially contribute to the existing knowledge and will have an impact on societies, since early stimulation of brain development might have long lasting consequences on cognitive performance, academic achievement and in the prevention of behavioural problems and the promotion of psychological adjustment and mental health. Clinical trials. Gov identifier: NCT02295072.