High muscular fitness level may positively affect bone strength and body composition in children with overweight and obesity.

Muscular fitness plays a major role in bone health and body composition in overweight and obese children. It is key that the development of this muscle fitness is affected by absolute isometric strength and dynamic strength. PURPOSE: To compare bone health and body composition between overweight/obese children considering muscular fitness (MF) levels, and to investigate whether weight-bearing dynamic or absolute isometric strength, both involved in the development of this muscular fitness, are more related with bone health. METHODS: MF of 59 overweight or obese children (10.1 ± 0.9 years, 27 females) was measured by a countermovement jump (CMJ), handgrip, and maximal isometric strength of knee extension. Participants were divided into four groups depending on their MF level performing a cluster analysis: 16 children with high MF (HMF) in all tests, 18 with high performance in isometric strength (HIS), 15 with high performance in CMJ (HCMJ) and 10 low isometric and low dynamic force values (LMF). Body composition values were measured by dual energy X-ray absorptiometry, and bone strength values were assessed by peripheral quantitative computed tomography. Motor skills were evaluated using TGMD-3. Multivariate analysis of covariance test was applied to analyse bone strength differences between children in the different MF groups, using maturity offset, height and weight as covariates, and correlations were investigated. RESULTS: HMF excelled in bone health. HIS had higher cortical bone area, periosteal circumference, bone mass, polar strength strain index and fracture load than LMF, while HCMJ only showed better results in trabecular bone area than LMF. HMF had significantly better values of fracture load and periosteal and endosteal circumferences than HCMJ, but not than HIS. CONCLUSIONS: High MF level shows positive effects on bone health in overweight/obese children. Those with highest isometric strength had better bone health compared to those with higher dynamic strength. TRIAL REGISTRATION: The research project was registered in a public database Clinicaltrials.gov in June 2020 with the identification number NCT04418713.

Bone metabolism in children with normal weight and overweight/obesity in a northeastern region of Spain.

Objectives: Bone mass progressively increases to peak during childhood and adolescence, which determines future bone health. Bone formation-resorption processes are assessed using bone markers. However, studies on the impact of obesity on bone turnover markers at this age are limited, and results are inconsistent. The objective of this study was to examine the potential impact of overweight/obesity on bone metabolism. Methods: A study was performed to compare parameters of bone metabolism in 45 girls and boys with normal weight (controls) and in a group of 612 girls and boys with overweight/obesity (cases) from the Exergames study (University of Zaragoza). Ages ranged from 8 to 12 years. Results: Higher values of phosphorus and IGFBP-3 were observed in children with overweight/obesity, as compared to children with normal weight, (p=0.042) and (p=0.042), respectively. BAP, osteocalcin, magnesium, vitamin D and IGF-I concentrations were lower in the group with overweight/obesity, whereas calcium concentrations were higher in this group, although differences were not statistically significant. A negative correlation was found (r=-0.193) (p=0.049) between BAP and BMI. Conclusions: Although differences did not reach statistical significance, BAP and osteocalcin concentrations were lower in children with overweight/obesity. This added to the negative correlation found between BAP and MIC may demonstrate that overweight/obesity may negatively affect bone health already at a young age.

Effect of an Active Video Game Intervention Combined With Multicomponent Exercise for Cardiorespiratory Fitness in Children With Overweight and Obesity: Randomized Controlled Trial.

BACKGROUND: Childhood overweight and obesity have become major global health problems and are negatively related with the cardiorespiratory fitness (CRF) level in school children and adolescents. Exercise, specifically multicomponent training, is effective for CRF improvement, but the main challenge is to ensure adherence to exercise in children with overweight and obesity. Therefore, new ways of exercising that are more attractive and motivational for this population are needed and playing or training with active video games (AVGs) has been proposed as an effective alternative because they require full-body movement and therefore increase energy expenditure. OBJECTIVE: The main aim of this study was to investigate the effects of an AVG intervention combined with multicomponent training on CRF at maximal and submaximal intensities in children with overweight or obesity. METHODS: We recruited 28 children (13 girls and 15 boys) aged 9 to 11 years with overweight or obesity from medical centers and divided them into 2 groups, an intervention group (n=20) that participated in a 5-month supervised AVG exercise program combined with multicomponent exercise, and a control group (n=8) that continued daily activities without modification. A maximal stress test to measure CRF using a walking-graded protocol with respiratory gas exchange was performed by the participants. RESULTS: The AVG group showed a significant decrease in heart rate and oxygen uptake for the same intensities in the submaximal stages of the maximal treadmill test, as well as a lower oxygen uptake percentage according to the individual maximal oxygen uptake, whereas the control group did not show overall changes. No change in the peak oxygen uptake (VO2peak) was found. CONCLUSIONS: A 5-month AVG intervention combined with multicomponent exercise had positive effects on CRF at submaximal intensity, showing a lower heart rate and oxygen uptake at the same intensities and displaying a lower oxygen uptake percentage according to the individual (VO2peak). Greater benefits were found in children with the highest fat percentage. TRIAL REGISTRATION: ClinicalTrials.gov NCT04418713; https://clinicaltrials.gov/show/NCT04418713.

Active Video Games Improve Muscular Fitness and Motor Skills in Children with Overweight or Obesity.

(1) Background: Childhood obesity is an important public health problem. Children with overweight or obesity often tend to show the pediatric inactivity triad components; these involve exercise deficit disorder, pediatric dynapenia, and physical illiteracy. The aim of the study was to examine the influence of an active video games (AVG) intervention combined with multicomponent exercise on muscular fitness, physical activity (PA), and motor skills in children with overweight or obesity. (2) Methods: A total of 29 (13 girls) children (10.07 ± 0.84 years) with overweight or obesity were randomly allocated in the intervention group (AVG group; n = 21) or in the control group (CG; n = 8). The intervention group performed a 5-month AVG training using the Xbox 360® with the Kinect, the Nintendo Wii®, dance mats, and the BKOOL® interactive cycling simulator, combined with multicomponent exercise, performing three sessions per week. The control group continued their daily activities without modification. Weight, PA using accelerometers, and motor competence using the Test of Gross Motor Development 3rd edition were measured. Muscular fitness was evaluated through the Counter Movement Jump height, maximal isometric strength of knee extension and handgrip strength, and lean mass using Dual-energy X-ray Absorptiometry. Mann−Whitney U and Wilcoxon signed rank tests were performed. The biserial correlation coefficients (r) were calculated. Spearman's correlation coefficients among PA, muscular fitness, and motor competence variables were also calculated. (3) Results: The AVG group significantly increased their knee extension maximal isometric strength (4.22 kg; p < 0.01), handgrip strength (1.93 kg; p < 0.01), and jump height (1.60 cm; p < 0.01), while the control group only increased the knee extension maximal isometric strength (3.15 kg; p < 0.01). The AVG group improved motor competence and light physical activity (p < 0.05) and decreased sedentary time (p < 0.05). Lean mass improved in both AVG group and CG (p < 0.05). Lastly, the percentage of improvement of motor skills positively correlated with the percentage of improvement in vigorous PA (r = 0.673; p = 0.003) and the percentage of improvement in CMJ (r = 0.466; p = 0.039). (4) Conclusions: A 5-month intervention combining AVG with multicomponent training seems to have positive effects on muscle fitness, motor competence, and PA in children with overweight or obesity.

A Cross-Sectional Study to Measure Physical Activity with Accelerometry in ADHD Children according to Presentations.

(1) Background: Attention deficit hyperactivity disorder (ADHD) is a common mental disorder affecting 5-7% of school-aged children. Previous studies have looked at the effects of physical activity interventions on the symptoms of ADHD, although few have compared the motor behavior of children with ADHD versus those without. This exploratory study provides detailed information on the patterns and intensity of physical activity and sedentary behavior in children with ADHD as measured by Actigraph GT3X accelerometry, as well as the differences in physical activity in the different presentations of ADHD; (2) Methods: A cross-sectional design was used with a sample of 75 children, aged 6 to 12 years, with and without ADHD. The ADHD group had a previous diagnosis, determined by clinical assessment based on DSM-5 criteria; (3) Results: Physical activity levels were higher in children with ADHD compared to children without ADHD, but there was no difference in sedentary time between groups during weekdays or weekends. Physical activity decreased with age, with significant differences in the ADHD group, who exhibited more minutes of moderate Physical activity in 6-7 year-olds than 10-11 year-olds during weekdays and weekends; (4) Conclusions: Sedentary time increased by age in children without ADHD, and there was a decrease in moderate-intensity physical activity time in children with ADHD by age.

25-Hydroxyvitamin D and Cardiorespiratory Fitness in Prepubertal Overweight and Obese Children.

Childhood obesity has become a major global health problem. Vitamin D deficiency and poor cardiorespiratory fitness are highly prevalent in children with overweight or obesity, but little is known about their relationships. In this study, we aimed to analyze the relationship between serum 25-hydroxyvitamin D (25(OH)D) and cardiorespiratory fitness parameters in prepubertal obese and overweight children. A cross-sectional design with a sample of 57 prepubertal children, aged 9-11 years, with overweight or obesity was used. The fasting concentration of 25(OH)D was analyzed with a chemiluminescent microparticle immunoassay. Fat and lean body masses were determined by using DXA. Maximal oxygen uptake (VO2max) was measured with the maximal treadmill test. A total of 68.4% of the sample had sufficient levels of 25(OH)D. As expected, their cardiorespiratory fitness was poor compared with that of normal-weight children, but 60% of the group exceeded the median obesity-specific reference values. No differences were found between the sexes for relative VO2max or 25(OH)D levels. Moreover, no correlations were found between 25(OH)D and body composition or cardiorespiratory parameters for sex or vitamin D groups. Vitamin D status seems not to be directly related to body composition or cardiorespiratory fitness in prepubertal overweight or obese children.

Effects of Sleep on the Academic Performance of Children with Attention Deficit and Hyperactivity Disorder.

Attention deficit and hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep and the association of sleep problems with ADHD is complex and multidirectional. The purpose of this study was to analyze the relationship between sleep and academic performance, comparing children with ADHD and a control group without ADHD. Academic performance in Spanish, mathematics, and a foreign language (English) was evaluated. Different presentations of ADHD were considered as well as the potential difference between weekday and weekend sleep habits. The sample consisted of 75 children aged 6-12 in primary education. Accelerometry was used to study sleep, and school grades were used to gather information about academic performance. The results showed that ADHD influenced the amount of sleep during weekends, the time getting up at the weekends, weekday sleep efficiency, as well as academic performance. Given the effects that were seen in the variables linked to the weekend, it is necessary to consider a longitudinal design with which to determine if there is a cause and effect relationship.

Assessment of Active Video Games' Energy Expenditure in Children with Overweight and Obesity and Differences by Gender.

(1) Background: Childhood obesity has become a main global health problem and active video games (AVG) could be used to increase energy expenditure. The aim of this study was to investigate the energy expenditure during an AVG intervention combined with exercise, differentiating by gender. (2) Methods: A total of 45 children with overweight or obesity (19 girls) performed an AVG intervention combined with exercise. The AVG used were the Xbox Kinect, Nintendo Wii, dance mats, BKOOL cycling simulator, and Nintendo Switch. The energy expenditure was estimated from the heart rate recorded during the sessions and the data from the individual maximal tests. (3) Results: The mean energy expenditure was 315.1 kilocalories in a one-hour session. Participants spent the most energy on BKOOL, followed by Ring Fit Adventures, Dance Mats, Xbox Kinect, and the Nintendo Wii, with significant differences between BKOOL and the Nintendo Wii. Significant differences between boys and girls were found, but were partially due to the difference in weight, VO2max, and fat-free mass. (4) Conclusions: The energy expenditure with AVG combined with multi-component exercise was 5.68 kcal/min in boys and 4.66 kcal/min in girls with overweight and obesity. AVG could be an effective strategy to increase energy expenditure in children and adolescents with overweight and obesity.

A systematic review of acute exercise as a coadjuvant treatment of ADHD in young people.

BACKGROUND: There are studies that show preliminary evidence of the benefits of physical exercise for people with Attention Deficit Hyperactivity Disorder (ADHD). The objective of the research being reported here was to carry out a systematic review of articles relating to the effects that exercise sessions have on children and adolescents with this pathology. METHOD: The total sample of studies considered was 1,723, of which only 11 met the eligibility criteria. RESULTS: The research included in this review showed that children with ADHD undertaking exercise experienced improvements in their characteristic symptoms, mainly attention deficit and hyperactivity, in comparison to other sedentary tasks such as watching a video. Five minutes of jumping or thirty minutes on a treadmill or static bicycle were enough to produce appreciable improvements in inhibitory control or in cognitive and executive functions. Benefits following exercise were also seen in other aspects such as reaction times and preparation for response, motor skills or brain activity. CONCLUSION: The findings make us optimistic that in the future physical exercise may become an alternative, or at least an effective complement, to the pharmacological treatments currently used for this pathology.

Secreted amyloid precursor protein and holo-APP bind amyloid beta through distinct domains eliciting different toxic responses on hippocampal neurons.

Amyloid beta (Abeta) is a metabolic product of Abeta precursor protein (APP). Deposition of Abeta in the brain and neuronal degeneration are characteristic hallmarks of Alzheimer's disease (AD). Abeta induces neuronal degeneration, but the mechanism of neurotoxicity remains elusive. Increasing evidence implicates APP as a receptor-like protein for Abeta fibrils (fAbeta). In this study, we present further experimental support for the direct interaction of APP with fAbeta and for its involvement in Abeta neurotoxicity. Using recombinant purified holo-APP (h-APP), we have shown that it directly binds fAbeta. Employing deletion mutant forms of APP, we show that two different sequences are involved in the binding of APP to fAbeta. One sequence in the n-terminus of APP is required for binding of fAbeta to secreted APP (s-APP) but not to h-APP. In addition, the extracellular juxtamembrane Abeta-sequence mediates binding of fAbeta to h-APP but not to s-APP. Deletion of the extracellular juxtamembrane Abeta sequence abolishes abnormal h-APP accumulation and toxicity induced by fAbeta deposition, whereas deletions in the n-terminus of APP do not affect Abeta toxicity. These experiments show that interaction of toxic Abeta species with its membrane-anchored parental protein promotes toxicity in hippocampal neurons, adding further support to an Abeta-receptor-like function of APP directly implicated in neuronal degeneration in AD.

cAMP-stimulated protein phosphatase 2A activity associated with muscle A kinase-anchoring protein (mAKAP) signaling complexes inhibits the phosphorylation and activity of the cAMP-specific phosphodiesterase PDE4D3.

The concentration of the second messenger cAMP is tightly controlled in cells by the activity of phosphodiesterases. We have previously described how the protein kinase A-anchoring protein mAKAP serves as a scaffold for the cAMP-dependent protein kinase PKA and the cAMP-specific phosphodiesterase PDE4D3 in cardiac myocytes. PKA and PDE4D3 constitute a negative feedback loop whereby PKA-catalyzed phosphorylation and activation of PDE4D3 attenuate local cAMP levels. We now show that protein phosphatase 2A (PP2A) associated with mAKAP complexes is responsible for reversing the activation of PDE4D3 by catalyzing the dephosphorylation of PDE4D3 serine residue 54. Mapping studies reveal that a C-terminal mAKAP domain (residues 2085-2319) binds PP2A. Binding to mAKAP is required for PP2A function, such that deletion of the C-terminal domain enhances both base-line and forskolin-stimulated PDE4D3 activity. Interestingly, PP2A holoenzyme associated with mAKAP complexes in the heart contains the PP2A targeting subunit B56delta. Like PDE4D3, B56delta is a PKA substrate, and PKA phosphorylation of mAKAP-bound B56delta enhances phosphatase activity 2-fold in the complex. Accordingly, expression of a B56delta mutant that cannot be phosphorylated by PKA results in increased PDE4D3 phosphorylation. Taken together, our findings demonstrate that PP2A associated with mAKAP complexes promotes PDE4D3 dephosphorylation, serving both to inhibit PDE4D3 in unstimulated cells and also to mediate a cAMP-induced positive feedback loop following adenylyl cyclase activation and B56delta phosphorylation. In general, PKA.PP2A.mAKAP complexes exemplify how protein kinases and phosphatases may participate in molecular signaling complexes to dynamically regulate localized intracellular signaling.

An adenylyl cyclase-mAKAPbeta signaling complex regulates cAMP levels in cardiac myocytes.

Protein kinase A-anchoring proteins (AKAPs) play important roles in the compartmentation of cAMP signaling, anchoring protein kinase A (PKA) to specific cellular organelles and serving as scaffolds that assemble localized signaling cascades. Although AKAPs have been recently shown to bind adenylyl cyclase (AC), the functional significance of this association has not been studied. In cardiac myocytes, the muscle protein kinase A-anchoring protein beta (mAKAPbeta) coordinates cAMP-dependent, calcium, and MAP kinase pathways and is important for cellular hypertrophy. We now show that mAKAPbeta selectively binds type 5 AC in the heart and that mAKAPbeta-associated AC activity is absent in AC5 knock-out hearts. Consistent with its known inhibition by PKA phosphorylation, AC5 is inhibited by association with mAKAPbeta-PKA complexes. AC5 binds to a unique N-terminal site on mAKAP-(245-340), and expression of this peptide disrupts endogenous mAKAPbeta-AC association. Accordingly, disruption of mAKAPbeta-AC5 complexes in neonatal cardiac myocytes results in increased cAMP and hypertrophy in the absence of agonist stimulation. Taken together, these results show that the association of AC5 with the mAKAPbeta complex is required for the regulation of cAMP second messenger controlling cardiac myocyte hypertrophy.

Amyloid-beta precursor protein mediates neuronal toxicity of amyloid beta through Go protein activation.

Amyloid beta (Abeta) is a metabolic product of amyloid-beta precursor protein (APP). Deposition of Abeta in the brain and neuronal degeneration are characteristic hallmarks of Alzheimer's disease (AD). Abeta induces neuronal degeneration, but the mechanism of neurotoxicity remains elusive. Here we show that overexpression of APP renders hippocampal neurons vulnerable to Abeta toxicity. Deletion of the extracellular Abeta sequence of APP prevents binding of APP to Abeta, and abolishes toxicity. Abeta toxicity is also abrogated by deletion of the cytoplasmic domain of APP, or by deletions comprising the Go protein-binding sequence of APP. Treatment with Pertussis toxin (PTX) abrogates APP-dependent toxicity of Abeta. Overexpression of PTX-insensitive Galpha-o subunit, but not Galpha-i subunit, of G protein restores Abeta toxicity in the presence of PTX, and this requires the integrity of APP-binding site for Go protein. Altogether, these experiments indicate that interaction of APP with toxic Abeta-species promotes toxicity in hippocampal neurons by a mechanism that involves APP-mediated Go protein activation, revealing an Abeta-receptor-like function of APP directly implicated in neuronal degeneration in AD.

Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: a potential mechanism of neuronal dystrophy in Alzheimer's disease.

Deposition of fibrillar amyloid beta (fAbeta) plays a critical role in Alzheimer's disease (AD). We have shown recently that fAbeta-induced dystrophy requires the activation of focal adhesion proteins and the formation of aberrant focal adhesion structures, suggesting the activation of a mechanism of maladaptative plasticity in AD. Focal adhesions are actin-based structures that provide a structural link between the extracellular matrix and the cytoskeleton. To gain additional insight in the molecular mechanism of neuronal degeneration in AD, here we explored the involvement of LIM kinase 1 (LIMK1), actin-depolymerizing factor (ADF), and cofilin in Abeta-induced dystrophy. ADF/cofilin are actin-binding proteins that play a central role in actin filament dynamics, and LIMK1 is the kinase that phosphorylates and thereby inhibits ADF/cofilin. Our data indicate that treatment of hippocampal neurons with fAbeta increases the level of Ser3-phosphorylated ADF/cofilin and Thr508-phosphorylated LIMK1 (P-LIMK1), accompanied by a dramatic remodeling of actin filaments, neuritic dystrophy, and neuronal cell death. A synthetic peptide, S3 peptide, which acts as a specific competitor for ADF/cofilin phosphorylation by LIMK1, inhibited fAbeta-induced ADF/cofilin phosphorylation, preventing actin filament remodeling and neuronal degeneration, indicating the involvement of LIMK1 in Abeta-induced neuronal degeneration in vitro. Immunofluorescence analysis of AD brain showed a significant increase in the number of P-LIMK1-positive neurons in areas affected with AD pathology. P-LIMK1-positive neurons also showed early signs of AD pathology, such as intracellular Abeta and pretangle phosphorylated tau. Thus, LIMK1 activation may play a key role in AD pathology.

Deposition of amyloid fibrils promotes cell-surface accumulation of amyloid beta precursor protein.

Amyloid beta protein (Abeta) deposition and neuronal degeneration are characteristic pathological features of Alzheimer's disease (AD). In vitro, Abeta fibrils (fAbeta) induce neuronal degeneration reminiscent to AD, but the mechanism of neurotoxicity is unknown. Here we show that amyloid fibrils increase the level of cell-surface full-length amyloid beta precursor protein (h-AbetaPP) and secreted AbetaPP (s-AbetaPP). Pulse-chase analysis indicated that fAbeta selectively inhibited the turnover of cell-surface AbetaPP, without altering its intracellular levels. FAbeta-induced AbetaPP accumulation was not abrogated by cycloheximide, suggesting that increased protein synthesis is not critically required. Abeta fibrils sequester s-AbetaPP from the culture medium and promote its accumulation at the cell surface, indicating that binding of Abeta fibrils mediates AbetaPP accumulation. A time course analysis of Abeta treatment showed that AbetaPP level is elevated before significant cell death can be detected, while other toxic insults do not augment AbetaPP level, suggesting that AbetaPP may be specifically involved in early stages of Abeta-induced neurodegeneration. Finally, Abeta fibrils promote clustering of h-AbetaPP in abnormal focal adhesion-like (FA-like) structures that mediate neuronal dystrophy, increasing its association with the cytoskeleton. These results indicate that the interaction of Abeta fibrils with AbetaPP is an early event in the mechanism of Abeta-induced neurodegeneration that may play a significant role in AD pathogenesis.