Association of Physical Fitness and Anthropometric Parameters With Lung Function in 7-Year-Old Children.

PURPOSE: Associations between health-related parameters and lung function remain unclear in childhood. The study aims to evaluate the relationship between physical fitness and anthropometric parameters with the lung function of healthy scholar-aged children. METHOD: A total of 418 children aged 7 years old participated in this study. The associations of physical fitness (handgrip strength, standing broad jump, and 800-m run) and anthropometric (waist circumference and body mass index) parameters with lung function (forced vital capacity and forced expiratory volume in 1 s) were analyzed using a mixed-linear regression model. RESULTS: Girls had significantly lower forced vital capacity values (P = .006) and physical fitness (P < .030) compared to boys. On mixed-linear regression analyses, waist circumference (P = .003) was independently associated with forced vital capacity, explaining 34.6% of its variance, while handgrip strength (P = .042) and waist circumference (P = .010) were independently associated with forced expiratory volume in 1 second, accounting together for 26.5% of its variance in 7-year-old healthy children. CONCLUSIONS: Handgrip strength and waist circumference were associated with lung function in healthy children highlighting the influence of upper body muscular strength and trunk dimension on lung function. Our results corroborate the need to promote physical fitness during childhood to protect against lung complications in later on in life.

Gestational Caloric Restriction Alters Adipose Tissue Methylome and Offspring's Metabolic Profile in a Swine Model.

Limited nutrient supply to the fetus results in physiologic and metabolic adaptations that have unfavorable consequences in the offspring. In a swine animal model, we aimed to study the effects of gestational caloric restriction and early postnatal metformin administration on offspring's adipose tissue epigenetics and their association with morphometric and metabolic variables. Sows were either underfed (30% restriction of total food) or kept under standard diet during gestation, and piglets were randomly assigned at birth to receive metformin (n = 16 per group) or vehicle treatment (n = 16 per group) throughout lactation. DNA methylation and gene expression were assessed in the retroperitoneal adipose tissue of piglets at weaning. Results showed that gestational caloric restriction had a negative effect on the metabolic profile of the piglets, increased the expression of inflammatory markers in the adipose tissue, and changed the methylation of several genes related to metabolism. Metformin treatment resulted in positive changes in the adipocyte morphology and regulated the methylation of several genes related to atherosclerosis, insulin, and fatty acids signaling pathways. The methylation and gene expression of the differentially methylated FASN, SLC5A10, COL5A1, and PRKCZ genes in adipose tissue associated with the metabolic profile in the piglets born to underfed sows. In conclusion, our swine model showed that caloric restriction during pregnancy was associated with impaired inflammatory and DNA methylation markers in the offspring's adipose tissue that could predispose the offspring to later metabolic abnormalities. Early metformin administration could modulate the size of adipocytes and the DNA methylation changes.

Physical Exercise-Induced DNA Methylation in Disease-Related Genes in Healthy Adults-A Systematic Review With Bioinformatic Analysis.

ABSTRACT: Vasileva, F, Hristovski, R, Font-Lladó, R, Georgiev, G, Sacot, A, López-Ros, V, Calleja-González, J, Barretina-Ginesta, J, López-Bermejo, A, and Prats-Puig, A. Physical exercise-induced DNA methylation in disease-related genes in healthy adults-A systematic review with bioinformatic analysis. J Strength Cond Res 38(2): 384-393, 2024-This study aimed to systematically review the existing literature regarding physical exercise (PE) and DNA methylation (DNAm) in healthy adults. Specific goals were to (a) identify differently methylated genes (DMGs) after PE intervention, their imprinting status, chromosome and genomic location, function, and related diseases; and (b) to screen for core genes and identify methylation changes of the core genes that can be modified by PE intervention. Our search identified 2,869 articles from which 8 were finally included. We identified 1851 DMGs ( p < 0.05) after PE intervention, although 45 of them were imprinted. Aerobic exercise (AE) seems to induce more DNA hypermethylation rather than hypomethylation, whereas anaerobic exercise (AN) seems to induce more DNA hypomethylation rather than hypermethylation. Aerobic exercise induced highest % of methylation changes on chromosome 6, whereas AN and mixed type (MT) on chromosome 1. Mixed type induced higher % of methylation changes close to transcription start site in comparison to AE and AN. After PE intervention, DMGs were mainly involved in fat metabolism, cell growth, and neuronal differentiation, whereas diseases regulated by those genes were mainly chronic diseases (metabolic, cardiovascular, neurodegenerative). Finally, 19 core genes were identified among DMGs, all related to protein metabolism. In conclusion, our findings may shed some light on the mechanisms explaining PE-induced health benefits such as the potential role that PE-induced DNAm may have in disease prevention and disease treatment.

Children's foot parameters and basic anthropometry - do arch height and midfoot width change?

The aims of this study were as follows: (1) to assess how foot posture and morphology assessments change according to body mass index (BMI) status; (2) to determine which body composition parameter (BMI or waist circumference) correlates better with the foot posture index (FPI), arch height index (AHI), and midfoot width (MFW) in children. Foot morphometry (FPI, AHI, and MFW) and body composition (BMI and waist circumference (WC)) were assessed in a cross-sectional study of 575 children (mean age = 7.42 ± 1.67 years; 53.27% female). When comparing BMI groups, an increase of 8.3% in AHI and 13.6% in MFW (both p < 0.0001) was seen. In linear regression analyses, BMI and WC were positively associated with MFW explaining together 64.8% of its variance. Noteworthy, MFW is the most related to body composition parameters. CONCLUSION: Foot morphology assessed by FPI, AHI, and MFW differs among BMI categories in children. Noteworthy, WC correlates better with foot measures than does the more commonly used BMI, and more importantly the MFW is the foot measure best explained by children's body weight. Since foot morphometry is different among different BMI groups, children would benefit from shoes with different patterns (thinner and wider), as well as a good system to adjust midfoot height. WHAT IS KNOWN: • Children who are overweight and obese have flatter feet, when assessed using footprints. • Up to 72% of people have incorrectly fitted shoes. WHAT IS NEW: • Children with underweight have thinner and flatter feet than children with normal weight, while children with overweight and obesity have wider and higher arched feet. • Body weight is related to foot shape, which has relevance for footwear manufacturers.

Metabolic programming in the offspring after gestational overfeeding in the mother: toward neonatal rescuing with metformin in a swine model.

OBJECTIVES: Maternal overfeeding during gestation may lead to adverse metabolic programming in the offspring mediated by epigenetic alterations. Potential reversal, in early life, of these alterations may help in the prevention of future cardio-metabolic conditions. In this context, our aims were: (1) to study the effects of maternal overfeeding on the metabolic and epigenetic programming of offspring's adipose tissue; and (2) to test the potential of postnatal metformin treatment to reverse these changes. METHODS: We used a swine animal model where commercial production sows were either overfed or kept under standard diet during gestation, and piglets at birth were randomly assigned to metformin (n = 16 per group) or vehicle treatment during lactation (n = 16 per group). RESULTS: Piglets born to overfed sows showed a worse metabolic profile (higher weight, weight gain from birth and abdominal circumference; all p < 0.05) together with altered serological markers (increased HOMA-IR, fructosamine, total cholesterol, C-Reactive Protein and lower HMW adiponectin; all p < 0.05). The visceral adipose tissue also showed altered morphology (increased adipocyte area, perimeter and diameter; all p < 0.05), as well as changes in gene expression (higher CCL2 and INSR, lower DLK1; all p < 0.05), and in DNA methylation (96 hypermethylated and 99 hypomethylated CpG sites; FDR < 0.05). Metformin treatment significantly ameliorated the abnormal metabolic profile, decreasing piglets' weight, weight gain from birth, abdominal circumference and fructosamine (all p < 0.05) and reduced adipocyte area, perimeter, and diameter in visceral adipose tissue (all p < 0.05). In addition, metformin treatment potentiated several associations between gene expression in visceral adipose tissue and the altered metabolic markers. CONCLUSIONS: Maternal overfeeding during gestation leads to metabolic abnormalities in the offspring, including adipose tissue alterations. Early metformin treatment mitigates these effects and could help rescue the offspring's metabolic health.

Catch-up growth in juvenile rats, fat expansion, and dysregulation of visceral adipose tissue.

BACKGROUND: Accelerated catch-up growth following intrauterine restriction increases the risk of developing visceral adiposity and metabolic abnormalities. However, the underlying molecular mechanisms of such metabolic programming are still poorly understood. METHODS: A Wistar rat model of catch-up growth following intrauterine restriction was used. A gene expression array was performed in the retroperitoneal adipose tissue sampled at postnatal day (PD) 42. RESULTS: Five hundred and forty-six differentially expressed genes (DEGs) were identified (adjusted p value < 0.05). Gene ontology enrichment analysis identified pathways related to immune and lipid metabolic processes, brown fat cell differentiation, and regulation of PI3K. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups (all p < 0.01) and related to several fat expansion and metabolic parameters, including body weight at PD42, postnatal body weight gain, white and brown adipose tissue mass, plasma triglycerides, and insulin resistance index (all p < 0.05). CONCLUSIONS: Genes related to immune and metabolic processes were upregulated in retroperitoneal adipose tissue following catch-up growth in juvenile rats and were found to be associated with fat expansion and metabolic parameters. Our results provide evidence for several dysregulated genes in white adipose tissue that could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth. IMPACT: Catch-up growth presents several dysregulated genes in white adipose tissue related to metabolic abnormalities. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups and related to visceral fat expansion and metabolic parameters. Profiling and validation of these dysregulated genes in visceral adipose tissue could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth.

Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size.

OBJECTIVES: To study DNA methylation at the C19MC locus in the placenta and its association with (1) parental body size, (2) transmission of haplotypes for the C19MC rs55765443 SNP, and (3) offspring's body size and/or body composition at birth and in childhood. SUBJECTS AND METHODS: Seventy-two pregnant women-infant pairs and 63 fathers were included in the study. Weight and height of mothers, fathers and newborns were registered during pregnancy or at birth (n = 72). Placental DNA methylation at the C19MC imprinting control region (ICR) was quantified by bisulfite pyrosequencing. Genotyping of the SNP was performed using restriction fragment length polymorphisms. The children's body size and composition were reassessed at age 6 years (n = 32). RESULTS: Lower levels of placental C19MC methylation were associated with increased body size of mother, specifically with higher pregestational and predelivery weights and height of the mother (ß from -0.294 to -0.371; R2 from 0.04 to 0.10 and all p < 0.019), and with higher weight, height, waist and hip circumferences, and fat mass of the child (ß from -0.428 to -0.552; R2 from 0.33 to 0.56 and all p < 0.009). Parental transmission of the SNP did not correlate with an altered placental methylation status at the C19MC ICR. CONCLUSIONS: Increased maternal size is associated with reduced placental C19MC methylation, which, in turn, relate to larger body size of the child.

A Pedagogical Approach to Integrative Neuromuscular Training to Improve Motor Competence in Children: A Randomized Controlled Trail.

Font-Lladó, R, López-Ros, V, Montalvo, AM, Sinclair, G, Prats Puig, A, and Fort-Vanmeerhaeghe, A. A pedagogical approach to integrative neuromuscular training to improve motor competence in children: a RCT. J Strength Cond Res 34(11): 3078-3085, 2020-To assess the effectiveness of a pedagogical approach to an integrative neuromuscular training (INT) program as a warm-up in physical education (PE) lessons in healthy children: (a) to improve the level of motor competence (MC) and (b) to master fundamental motor skills (FMS) patterns, considering the baseline MC level and the time spent when performing different motor tasks. One hundred ninety students (7.43 ± 0.32 years; 52% girls) were included in this randomized controlled trail and grouped up according to MC basal levels (L1-L4). Motor competence and FMS patterns (CAMSA protocol) were assessed before and after the intervention in a group-based INT warm-up (n = 97) and a group-based conventional warm-up (n = 93). The INT program improved MC (p < 0.001; d = 0.71) and FMS (p < 0.001, d = 0.52). The independent predictors of MC change were: baseline MC level (ß = -196; p < 0.012), time spent to perform the task (ß = -0.235 p < 0.003), and participation in the INT program (ß = 0.201; p < 0.005), explaining 71% of its variability. The INT warm-up shows correlations between improvements in MC in relation to time reduction (L1 p = 0.016, d, L2 p = 0.001, and L4 = 0.001) and FMS patterns (L1 p < 0.001, L2 p < 0.003, L3 p < 0.005, and L4 < 0.001) Moreover, only L3, it showed correlation between changes in time and FMS mastery (p = 0.001). Our results showed that a pedagogical approach to an INT program developed as a warm-up in primary school PE lessons can improve MC and FMS patterns in all subjects, independent of the initial MC level. More interestingly, only in L3, the improvement in MC can be explained by the balance in time required to perform the task and the level of improvement in FMS patterns.

Dlk1 expression relates to visceral fat expansion and insulin resistance in male and female rats with postnatal catch-up growth.

BACKGROUND: Although prenatal and postnatal programming of metabolic diseases in adulthood is well established, the mechanisms underpinning metabolic programming are not. Dlk1, a key regulator of fetal development, inhibits adipocyte differentiation and restricts fetal growth. METHODS: Assess DLk1 expression in a Wistar rat model of catch-up growth following intrauterine restriction. Dams fed ad libitum delivered control pups (C) and dams on a 50% calorie-restricted diet delivered pups with low birth weight (R). Restricted offspring fed a standard rat chow showed catch-up growth (R/C) but those kept on a calorie-restricted diet did not (R/R). RESULTS: Decreased Dlk1 expression was observed in adipose tissue and skeletal muscle of R/C pups along with excessive visceral fat accumulation, decreased circulating adiponectin, increased triglycerides and HOMA-IR (from p < 0.05 to p < 0.0001). Moreover, in R/C pups the reduced Dlk1 expression in adipose tissue and skeletal muscle correlated with visceral fat (r = -0.820, p < 00001) and HOMA-IR (r = -0.745, p = 0.002). CONCLUSIONS: Decreased Dlk1 expression relates to visceral fat expansion and insulin resistance in a rat model of catch-up growth following prenatal growth restriction. Modulation of Dlk1 expression could be among the targets for the early prevention of fetal programming of adult metabolic disorders.

Serum 25-hydroxyvitamin D and cardiovascular disease risk factors in women with excessive weight gain during pregnancy and in their offspring at age 5-6 years.

BACKGROUND/OBJECTIVE: Low 25-hydroxyvitamin D levels [25(OH)D] may increase the risk for cardiovascular disease (CVD). In pregnant women excessive weight gain and 25(OH)D deficiency are common complications and both could have deleterious consequences on their children. We aimed to study the relationship between serum 25(OH)D and CVD risk factors in pregnant women and in their offspring at school age. SUBJECTS/METHODS: Fasting serum 25(OH)D and its bioavailable fraction were quantified in 310 healthy pregnant women [with adequate (n = 113), insufficient (n = 113) and excessive (n = 84) weight gain]. A follow-up at 5-6 years was performed in sixty-six children born of these mothers. Lipids, insulin, glucose, and high-sensitivity C-reactive protein (hsCRP) were measured in all subjects. Children's carotid intima-media thickness (cIMT) together with visceral and intra-abdominal fat were measured by ultrasonography. RESULTS: Lower maternal 25(OH)D concentrations were associated with lower maternal age, and higher body mass index, triglycerides and hsCRP (all p < 0.05). In women with excessive weight gain during gestation, serum 25(OH)D concentrations showed independent associations with maternal hsCRP (ß = -0.283 p = 0.03) and triglycerides (ß = -0.436, p = 0.005). Maternal serum 25(OH)D concentrations were also independently associated with cIMT (ß = -0.288, p = 0.04), visceral fat (ß = -0.281, p = 0.01) and intra-abdominal fat (ß = -0.248, p = 0.01) in their children at 5-6 years. CONCLUSIONS: Lower serum 25(OH)D concentrations were related to CVD risk factors in pregnant woman and in their offspring. The cardiometabolic consequences of low 25(OH)D concentrations during pregnancy could be aggravated by excessive weight gain during gestation.

The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal growth in humans.

BACKGROUND: The developmentally important DLK1-DIO3 imprinted domain on human chromosome 14 is regulated by 2 differentially methylated regions, the intergenic differentially methylated region and the MEG3 differentially methylated region. OBJECTIVE: The aim was to determine the natural variation in DNA methylation at these differentially methylated regions in human placentas, and to determine its link to gene expression levels at the domain. The second goal was to explore whether the domain's methylation and gene expression correlate with prenatal and early postnatal growth of the conceptus. STUDY DESIGN: Using pyrosequencing, we determined methylation levels at CpG dinucleotides across the 2 regulatory differentially methylated regions in placentas from 91 healthy mothers. At birth, placentas and infants were weighed (gestational age 39 ± 1 weeks; birthweight SD score 0.1 ± 0.8) and placental biopsies were collected. RNA expression was quantitated by real-time polymerase chain reaction. Infants' weights and lengths were followed up monthly during the first year. RESULTS: Methylation levels at the 2 regulatory differentially methylated regions were linked and varied considerably between placentas. MEG3 promoter differentially methylated region methylation correlated negatively with weight increase (ß = -0.406, P = .001, R2 = 0.206) and length increase (ß = -0.363, P = .002, R2 = 0.230) during the first postnatal year. The methylation level of the intergenic differentially methylated region correlated with DIO3 expression (ß = 0.313, P = .032, R2 = 0.152). Furthermore, the expression of both DIO3 and RTL1 (both imprinted genes within the DLK1-DIO3 domain) was negatively associated with birthweight (ß = -0.331, P = .002, R2 = 0.165; and ß = -0.307, P = .005, R2 = 0.159, respectively). RTL1 expression, in addition, was negatively linked to birth length (ß = -0.306, P = .007, R2 = 0.162). CONCLUSION: Our combined findings strongly suggest that placental DNA methylation at the DLK1-DIO3 domain's intergenic differentially methylated region and MEG3 promoter differentially methylated region relates to measures of early human growth, and may thus contribute to its control.

Serum Ferritin Relates to Carotid Intima-Media Thickness in Offspring of Fathers With Higher Serum Ferritin Levels.

OBJECTIVE: Body iron status has been linked to atherosclerosis in adults. The purposes of our study were to determine (1) the association between circulating ferritin levels and carotid intima-media thickness (cIMT) in a cohort of apparently healthy children and (2) the association between cIMT and parental ferritin levels. APPROACH AND RESULTS: Circulating ferritin levels (microparticle enzyme immunoassay), metabolic parameters, and cIMT (ultrasonography) were analyzed cross-sectionally in a cohort of 692 healthy white children with a mean age of 8 ± 2 years (52% girls and 48% boys). In consecutive 123 children from the cross-sectional sample, the same serum assessments were also performed at baseline in their parents, and the cIMT was repeated after 3 years of follow-up in the children at a mean age of 11 ± 2 years (53% girls and 47% boys). Weak but significant positive associations were evident between children's circulating ferritin levels and cIMT (r=0.123; P=0.001) and with the change in cIMT 3 years later a tendency was also observed (r=0.185; P=0.048). In multiple regression analyses, circulating ferritin levels contributed independently to cIMT variance (ß=0.090; P=0.026; R(2)=10%) and cIMT change variance (ß=0.216; P=0.019; R(2)= 3.4%) after controlling for body mass index, high-sensitivity C-reactive protein, age, sex, and low-density lipoprotein-cholesterol levels. This association was, however, remarkably significant (ß=0.509; P=0.001; R(2)= 20.4%) in children whose fathers had ferritin levels above the median value (122.5 ng/mL).The latter association remained significant after correction for multiple testing. Maternal's ferritin levels showed no interaction in this association. CONCLUSIONS: These results suggest a paternal-specific effect on cIMT partially reflected by father's ferritin levels.

Soluble CRTC3: A Newly Identified Protein Released by Adipose Tissue That Is Associated with Childhood Obesity.

BACKGROUND: CREB-regulated transcription coactivator 3 (CRTC3) is found in adipocytes, where it may promote obesity through disruption of catecholamine signaling. We wished to assess whether CRTC3 is a soluble protein secreted by adipose tissue, explore whether CRTC3 is detectable and quantifiable in the circulation, and ascertain whether CRTC3 serum concentrations are related to metabolic markers in children. METHODS: Explants of adipose tissue from 12 children were cultured to study adipocyte cell size and the secretion of CRTC3 (immunoblot and ELISA). We also performed a cross-sectional and longitudinal study in 211 asymptomatic prepubertal white children at age 7 years, 115 of whom were followed up at age approximately 10 years. We measured circulating concentrations of CRTC3 and studied associations between serum CRTC3 and metabolic markers. RESULTS: Measurable concentrations of CRTC3 were found in conditioned media of adipose tissue explants and in serum samples. CRTC3 concentrations in visceral adipose tissue were negatively associated with adipocyte cell size and positively related to adipocyte cell number (P < 0.05). In the cross-sectional study, higher CRTC3 concentrations were associated with higher body mass index (P = 0.001), waist circumference (P = 0.003), and systolic blood pressure (P = 0.007) and lower high molecular weight adiponectin (P = 0.003). In the longitudinal study, serum concentrations of CRTC3 at age approximately 7 years were associated with changes in waist circumference (ß = 0.254; P = 0.004; r = 0.145) and high molecular weight adiponectin (ß=-0.271; P = 0.014; r = 0.101), respectively, at age approximately 10 years. CONCLUSIONS: CRTC3, a newly identified protein that is related to childhood obesity, is present in the circulation, partly as a result of adipose tissue secretion. Higher serum CRTC3 concentrations are related to and predict a poorer metabolic profile in children.

Balanced duo of anti-inflammatory SFRP5 and proinflammatory WNT5A in children.

BACKGROUND: Secreted frizzled-related protein 5 (SFRP5) is an adipokine protecting against obesity-related insulin resistance and diabetes. SFRP5 binds to wingless type mouse mammary tumor virus (MMTV) integration site family member 5A (WNT5A) to improve insulin sensitivity. We performed the first study of SFRP5 and WNT5A simultaneously in children. METHODS: Prepubertal children (n = 342) were assessed for circulating SFRP5 (all subjects) and circulating WNT5A (210 subjects), and associations were sought with metabolic markers. In conditioned media of adipose tissue explants from 12 additional children, SFRP5 and WNT5A were studied further. RESULTS: The concentrations of SFRP5 and WNT5A correlated positively in serum and in conditioned media (all P < 0.001). Lower level of circulating SFRP5 (lowest quartile) was associated with higher BMI (15% increase, P < 0.0001) and lower level of high-molecular-weight adiponectin (26% decrease, P = 0.002). Circulating WNT5A related closely with insulin resistance assessed by the homeostasis model assessment for insulin resistance and hepatic markers (alanine transaminase and gamma glutamyl transpeptidase), particularly in children with lower circulating SFRP5 levels (all P < 0.004). CONCLUSION: SFRP5 and WNT5A comprise a balanced duo that may regulate metabolic homeostasis in prepubertal children.

Integrated neuromuscular training intervention applied in schools induces a higher increase in salivary high molecular weight adiponectin and a more favorable body mass index, cardiorespiratory fitness and muscle strength in children as compared to the traditional physical education classes.

Background: High-molecular-weight adiponectin (HMW-adiponectin) is a cardio-metabolic health protector. Objectives: (1) to compare body mass index (BMI), cardiorespiratory fitness (CRF) and muscle strength (MS) in healthy school-children depending on their baseline salivary-HMW-adiponectin concentration; and (2) to apply a 3-month integrated neuromuscular training (INT) and evaluate its effects on salivary-HMW-adiponectin concentration, BMI, CRF and MS in the same children. Additional goal: to identify if any potential changes during the 3-month period may be related to a potential change in salivary-HMW-adiponectin concentration. Methods: Ninety children (7.4 ± 0.3 years) were recruited in primary schools and randomly allocated into control or intervention group. The intervention consisted of a 3-month INT applied during physical education (PE) classes, twice-weekly, while the control group had traditional PE classes. Body mass and height were measured, BMI was calculated and HMW-adiponectin was quantified in saliva. To assess CRF and MS, 800 m-run and hand-dynamometry were applied, respectively. All measurements were performed twice, at baseline and after 3 months. Results: Children with higher baseline salivary-HMW-adiponectin have more favorable BMI (p = 0.006) and slightly higher CRF (p = 0.017) in comparison to the children with lower baseline salivary-HMW-adiponectin. There were no big changes after the 3-month-period neither in the control, nor the INT group. However, it is worthy to note that the INT induced slightly higher increase in salivary-HMW-adiponectin (p = 0.007), and a slightly higher improvement in BMI (p = 0.028), CRF (p = 0.043) and MS (p = 0.003), as compared to the traditional PE classes. Finally, the INT-induced improvement in CRF was associated with the increased post-salivary-HMW-adiponectin concentration (p = 0.022). Conclusion: Main findings may suggest the potential utility of an INT as a cost-effective strategy that can be applied in schools to induce cardio-protective effects in school-children.

Salivary cardiac-enriched FHL2-interacting protein is associated with higher diastolic-to-systolic-blood pressure ratio, sedentary time and center of pressure displacement in healthy 7-9 years old school-children.

Introduction: Cardiac-enriched FHL2-interacting protein (CEFIP) is a recently identified protein, first found in the z-disc of striated muscles, and related to cardiovascular diseases. Our objectives are: 1) to quantify CEFIP in saliva in healthy 7-9 years old school-children; and 2) to assess the associations of salivary CEFIP concentration and blood pressure, physical (in)activity and physical fitness in these children. Methods: A total of 72 children (7.6 ± 0.3 years) were included in the study, recruited in primary schools in Girona (Spain). A sandwich enzyme-linked immunosorbent assay was used (abx506878; Abbexa, United Kingdom) to quantify CEFIP in saliva. Anthropometric evaluation was performed [body mass, height and body mass index (BMI)]. Systolic and diastolic blood pressure were measured by means of an electronic oscillometer and the diastolic-to-systolic blood pressure ratio (D/S BP ratio) was calculated. Physical (in)activity [sedentary time and time spent in physical activity (PA)] were assessed by means of a triaxial Actigraph GT3X accelerometer (Actigraph, Pensacola, FL, USA) that children were instructed to wear for 24h during 7 conssecutive days. Finally, physical fitness (speed and agility, explosive power of legs, handgrip strength, flexibility and balance) were assessed through validated and standardized testing batteries. Results: CEFIP was easily detected and measured in all saliva samples (mean concentration: 0.6 ± 0.2 pg/ml). Salivary CEFIP was positively associated with D/S BP ratio (r=0.305, p=0.010) and sedentary time (r=0.317, p=0.012), but negatively associated with PA in 7-9 years old school-children (r=-0.350, p=0.002). Furthermore, salivary CEFIP was related to lower level of balance i.e., higher center of pressure (CoP) displacement in these children (r=0.411, p<0.001). The associations of salivary CEFIP with D/S BP ratio (Beta=0.349, p=0.004), sedentary time (Beta=0.354, p=0.009) and CoP displacement (Beta=0.401, p=0.001), were maintained significant after adjustment for potential confounding variables such as age, gender and BMI in linear regression analyses. Conclusion: CEFIP can be easily assessed in saliva as a promising biomarker associated with cardiovascular health in 7-9 years old school-children. Interestingly, higher salivary CEFIP concentration was related to higher D/S BP ratio, more sedentary time and higher CoP displacement i.e., lower level of balance in these children.

Insulin resistance, C-reactive protein, diastolic to systolic blood pressure ratio and epicardial fat are related to sedentary time, and inversely related to physical activity in school-aged children.

Background: Physical activity (PA) is beneficial for the overall health. Objectives are: (1) To compare metabolic (MRM) and cardiovascular-risk-markers (CRM) in children according to their PA-level; (2) to explore the associations of MRM and CRM with PA and sedentary time (ST); and (3) to identify the associations between MRM and CRM in less (LA) and more active (MA) children. Methods: A total of 238 apparently healthy school-aged children were enrolled (132 boys/106 girls; 9.1 ± 1.8 years) and body mass index standard deviation score (BMI SDS) and blood pressure were assessed. Fasting venous blood sampling was performed to assess insulin resistance (HOMA-IR) and high-sensitivity-C-reactive protein (hsCRP). Epicardial fat, interventricular septal and left ventricular posterior wall thicknesses were assessed by high-resolution ultrasonography. PA and ST were assessed by enKid-questionnaire. Children were classified based on enKid-score as being LA and MA (below and above 50th percentile for PA). Results: MA-children had lower values for: BMI SDS, diastolic-to-systolic blood pressure ratio, HOMA-IR and hsCRP (7.02 to 61.5% lower, p = 0.040 to p < 0.0001) compared to LA-children. MRM and CRM were positively associated with ST (p = 0.003 to p < 0.001), and negatively associated with PA (p = 0.044 to p < 0.001). Finally, MRM were positively associated with CRM (p = 0.008 to p < 0.0001). Interestingly, the latter associations were observed in LA-children but were not present in MA-children. Conclusion: More PA is associated with better cardio-metabolic profile in school-aged children. PA seems to modulate the associations between MRM and CRM, thus reinforcing the idea that fostering PA in children may lower the risk for development of a cardio-metabolic disease.

Iron status and cardiometabolic risk in children.

AIM: We aimed to evaluate associations between serum ferritin and transferrin and variables related to the metabolic syndrome (MetS) in children. METHODS: Cross-sectional and longitudinal study in prepubertal children (n = 832) aged 3-14 years. A subset (n = 203) were re-examined after a mean follow-up of 3.7 ± 0.8 years[range 2-6]. Outcomes were MetS and MetS components scores, glycosylated haemoglobin (HbA1c), and their follow-up change. RESULTS: Children with low ferritin had increased HbA1c Z scores (ANCOVA, P = 0.003). Ferritin was inversely associated with glycaemia [fully adjusted ß (95% confidence interval): -2.35(-4.36 to -0.34)]. Transferrin was associated with diastolic blood pressure [ß: 0.02(0.01-0.04)] and log-HOMA-IR [ß:0.001(0.0005-0.002)]. MetS risk score worsened during follow-up in children with the lowest baseline ferritin levels. In contrast, at baseline ferritin was positively associated with all (except glycaemia) the MetS-related variables but adjustments for inflammatory, hepatic function, and body mass markers attenuated those associations (P > 0.05). CONCLUSIONS: Lower iron status was independently associated with glycaemic markers and MetS in children, whereas higher ferritin levels were related to other cardiometabolic risk markers under the influence of inflammation, hepatic injury and body mass. Research is required to study whether this mixed pattern is part of an early risk or would be explained by a normal transition during growth and development.

Gestational Weight Gain Relates to DNA Methylation in Umbilical Cord, Which, In Turn, Associates with Offspring Obesity-Related Parameters.

Excessive gestational weight gain (GWG) has a negative impact on offspring's health. Epigenetic modifications mediate these associations by causing changes in gene expression. We studied the association between GWG and DNA methylation in umbilical cord tissue; and determined whether the DNA methylation and the expression of corresponding annotated genes were associated with obesity-related parameters in offspring at 6 years of age. The methylated CpG sites (CpGs) associated with GWG were identified in umbilical cord tissue by genome-wide DNA methylation (n = 24). Twelve top CpGs were validated in a wider sample by pyrosequencing (n = 87), and the expression of their 5 annotated genes (SETD8, TMEM214, SLIT3, RPTOR, and HOXC8) was assessed by RT-PCR. Pyrosequencing results validated the association of SETD8, SLIT3, and RPTOR methylation with GWG and showed that higher levels of SETD8 and RPTOR methylation and lower levels of SLIT3 methylation relate to a higher risk of obesity in the offspring. The association of SETD8 and SLIT3 gene expression with offspring outcomes paralleled the association of methylation levels in opposite directions. Epigenetic changes in the umbilical cord tissue could explain, in part, the relationship between GWG and offspring obesity risk and be early biomarkers for the prevention of overweight and obesity in childhood.