Eating disorders and obesity: bridging clinical, neurobiological, and therapeutic perspectives.

Eating disorders (EDs) and obesity are complex health conditions sharing various risk and maintenance factors, intensified in cases of comorbidity. This review explores the similarities and connections between these conditions, examining different facets from a multidisciplinary perspective, among them comorbidities, metabolic and psychological factors, neurobiological aspects, and management and therapy implications. We aim to investigate the common characteristics and complexities of weight and EDs and explore their interrelationships in individuals who experience both. The rising prevalence of EDs in people with obesity necessitates integrated approaches to study this comorbidity and to identify and analyze both common and distinct features of these conditions. This review may offer new opportunities for simultaneous prevention and management approaches, as well as future lines of research.

Psychosocial and environmental risk factors of obesity and hypertension in children and adolescents-a literature overview.

Childhood obesity has become a worldwide epidemic in the 21st century. Its treatment is challenging and often ineffective, among others due to complex, often not obvious causes. Awareness of the existence and meaning of psychosocial and environmental risk factors seems to be an essential element in the prevention and treatment of obesity and its complications, especially arterial hypertension. In this review, we will discuss the role of that risk factors linking obesity and increased cardiovascular disorders including the role of nutritional factors (including the role of unhealthy diet, inadequate hydration), unhealthy behaviors (e.g. smoking, alcohol and drugs, sedentary behavior, low physical activity, disrupted circadian rhythms, sleep disorders, screen exposure), unfavorable social factors (such as dysfunctional family, bullying, chronic stress, mood disorders, depression, urbanization, noise, and environmental pollution), and finally differences in cardiovascular risk in girls and boys.

Study protocol: Identification and validation of integrative biomarkers of physical activity level and health in children and adolescents (INTEGRActiv).

Background: Physical activity (PA) provides health benefits across the lifespan and improves many established cardiovascular risk factors that have a significant impact on overall mortality. However, discrepancies between self-reported and device-based measures of PA make it difficult to obtain consistent results regarding PA and its health effects. Moreover, PA may produce different health effects depending on the type, intensity, duration, and frequency of activities and individual factors such as age, sex, body weight, early life conditions/exposures, etc. Appropriate biomarkers relating the degree of PA level with its effects on health, especially in children and adolescents, are required and missing. The main objective of the INTEGRActiv study is to identify novel useful integrative biomarkers of PA and its effects on the body health in children and adolescents, who represent an important target population to address personalized interventions to improve future metabolic health. Methods/design: The study is structured in two phases. First, biomarkers of PA and health will be identified at baseline in a core cohort of 180 volunteers, distributed into two age groups: prepubertal (n = 90), and postpubertal adolescents (n = 90). Each group will include three subgroups (n = 30) with subjects of normal weight, overweight, and obesity, respectively. Identification of new biomarkers will be achieved by combining physical measures (PA and cardiorespiratory and muscular fitness, anthropometry) and molecular measures (cardiovascular risk factors, endocrine markers, cytokines and circulating miRNA in plasma, gene expression profile in blood cells, and metabolomics profiling in plasma). In the second phase, an educational intervention and its follow-up will be carried out in a subgroup of these subjects (60 volunteers), as a first validation step of the identified biomarkers. Discussion: The INTEGRActiv study is expected to provide the definition of PA and health-related biomarkers (PA-health biomarkers) in childhood and adolescence. It will allow us to relate biomarkers to factors such as age, sex, body weight, sleep behavior, dietary factors, and pubertal status and to identify how these factors quantitatively affect the biomarkers' responses. Taken together, the INTEGRActiv study approach is expected to help monitor the efficacy of interventions aimed to improve the quality of life of children/adolescents through physical activity. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT05907785.

Impact of Maternal Weight Gain on the Newborn Metabolome.

Pre-pregnancy obesity and excessive gestational weight gain (GWG) appear to affect birth weight and the offspring's risk of obesity and disease later in life. However, the identification of the mediators of this relationship, could be of clinical interest, taking into account the presence of other confounding factors, such as genetics and other shared influences. The aim of this study was to evaluate the metabolomic profiles of infants at birth (cord blood) and 6 and 12 months after birth to identify offspring metabolites associated with maternal GWG. Nuclear Magnetic Resonance (NMR) metabolic profiles were measured in 154 plasma samples from newborns (82 cord blood samples) and in 46 and 26 of these samples at 6 months and 12 months of age, respectively. The levels of relative abundance of 73 metabolomic parameters were determined in all the samples. We performed univariate and machine-learning analysis of the association between the metabolic levels and maternal weight gain adjusted for mother's age, Body Mass Index (BMI), diabetes, diet adherence and infant sex. Overall, our results showed differences, both at the univariate level and in the machine-learning models, between the offspring, according to the tertiles of maternal weight gain. Some of these differences were resolved at 6 and 12 months of age, whereas some others remained. Lactate and leucine were the metabolites with the strongest and longest association with maternal weight gain during pregnancy. Leucine, as well as other significant metabolites, have been associated in the past with metabolic wellness in both general and obese populations. Our results suggest that the metabolic changes associated to excessive GWG are present in children from early life.

Blood pressure response to exercise in children and adolescents.

Blood pressure changes during exercise are part of the physiological response to physical activity. Exercise stress testing can detect an exaggerated blood pressure response in children and adolescent. It is applied for certain clinical conditions, but is also commonly used as part of the assessment of athletes. The interpretation of blood pressure values in response to exercise during childhood and adolescence requires appropriate reference data. We discuss the available reference values and their limitations with regard to device, exercise protocol and normalization. While the link between an exaggerated blood pressure response and cardiovascular events and mortality has been demonstrated for adults, the situation is less clear for children and adolescents. We discuss the existing evidence and propose that under certain circumstances it might be reasonable to have children and adolescents undergo exercise stress testing as a rather non-invasive procedure to add additional information with regard to their cardiovascular risk profile. Based on the existing data future studies are needed to extend our current knowledge on possible links between the presence of certain clinical conditions, the detectability of an exaggerated blood pressure response during childhood and adolescence and the risk of developing cardiovascular morbidity and mortality in later life.

Are Peripheral Biomarkers Determinants of Eating Styles in Childhood and Adolescence Obesity? A Cross-Sectional Study.

Disturbances in eating behaviors have been widely related to obesity. However, little is known about the role of obesity-related biomarkers in shaping habitual patterns of eating behaviors (i.e., eating styles) in childhood. The objective of the present study was to explore the relationships between several biomarkers crucially involved in obesity (ghrelin, insulin resistance, and leptin/adiponectin ratio) and eating styles in children and adolescents with obesity. Seventy participants aged between 8 and 16 (56.2% men) fulfilled the Spanish version of the Dutch Eating Behavior Questionnaire for Children to measure external, emotional, and restrained eating styles. In addition, concentrations of ghrelin, leptin, adiponectin, insulin, and glucose were obtained through a blood test. Hierarchical multiple regression analyses controlling for age and sex were computed for each eating style. Results indicated that individuals with higher ghrelin concentration levels showed lower scores in restrained eating (ß = -0.61, p < 0.001). The total model explained 32% of the variance of the restrained pattern. No other relationships between obesity-related biomarkers and eating behaviors were found. This study highlights that one of the obesity-risk factors, namely lower plasma ghrelin levels, is substantially involved in a well-known maladaptive eating style, restraint eating, in childhood obesity.

Obesity and Cardiometabolic Risk Factors: From Childhood to Adulthood.

Obesity has become a major epidemic in the 21st century. It increases the risk of dyslipidemia, hypertension, and type 2 diabetes, which are known cardiometabolic risk factors and components of the metabolic syndrome. Although overt cardiovascular (CV) diseases such as stroke or myocardial infarction are the domain of adulthood, it is evident that the CV continuum begins very early in life. Recognition of risk factors and early stages of CV damage, at a time when these processes are still reversible, and the development of prevention strategies are major pillars in reducing CV morbidity and mortality in the general population. In this review, we will discuss the role of well-known but also novel risk factors linking obesity and increased CV risk from prenatal age to adulthood, including the role of perinatal factors, diet, nutrigenomics, and nutri-epigenetics, hyperuricemia, dyslipidemia, hypertension, and cardiorespiratory fitness. The importance of 'tracking' of these risk factors on adult CV health is highlighted and the economic impact of childhood obesity as well as preventive strategies are discussed.

Innovations in Infant Feeding: Future Challenges and Opportunities in Obesity and Cardiometabolic Disease.

The field of nutrition in early life, as an effective tool to prevent and treat chronic diseases, has attracted a large amount of interest over recent years. The vital roles of food products and nutrients on the body's molecular mechanisms have been demonstrated. The knowledge of the mechanisms and the possibility of controlling them via what we eat has opened up the field of precision nutrition, which aims to set dietary strategies in order to improve health with the greatest effectiveness. However, this objective is achieved only if the genetic profile of individuals and their living conditions are also considered. The relevance of this topic is strengthened considering the importance of nutrition during childhood and the impact on the development of obesity. In fact, the prevalence of global childhood obesity has increased substantially from 1990 and has now reached epidemic proportions. The current narrative review presents recent research on precision nutrition and its role on the prevention and treatment of obesity during pediatric years, a novel and promising area of research.

Development of a Minimally Invasive Screening Tool to Identify Obese Pediatric Population at Risk of Obstructive Sleep Apnea/Hypopnea Syndrome.

Obstructive sleep apnea syndrome is a reduction of the airflow during sleep which not only produces a reduction in sleep quality but also has major health consequences. The prevalence in the obese pediatric population can surpass 50%, and polysomnography is the current gold standard method for its diagnosis. Unfortunately, it is expensive, disturbing and time-consuming for experienced professionals. The objective is to develop a patient-friendly screening tool for the obese pediatric population to identify those children at higher risk of suffering from this syndrome. Three supervised learning classifier algorithms (i.e., logistic regression, support vector machine and AdaBoost) common in the field of machine learning were trained and tested on two very different datasets where oxygen saturation raw signal was recorded. The first dataset was the Childhood Adenotonsillectomy Trial (CHAT) consisting of 453 individuals, with ages between 5 and 9 years old and one-third of the patients being obese. Cross-validation was performed on the second dataset from an obesity assessment consult at the Pediatric Department of the Hospital General Universitario of Valencia. A total of 27 patients were recruited between 5 and 17 years old; 42% were girls and 63% were obese. The performance of each algorithm was evaluated based on key performance indicators (e.g., area under the curve, accuracy, recall, specificity and positive predicted value). The logistic regression algorithm outperformed (accuracy = 0.79, specificity = 0.96, area under the curve = 0.9, recall = 0.62 and positive predictive value = 0.94) the support vector machine and the AdaBoost algorithm when trained with the CHAT datasets. Cross-validation tests, using the Hospital General de Valencia (HG) dataset, confirmed the higher performance of the logistic regression algorithm in comparison with the others. In addition, only a minor loss of performance (accuracy = 0.75, specificity = 0.88, area under the curve = 0.85, recall = 0.62 and positive predictive value = 0.83) was observed despite the differences between the datasets. The proposed minimally invasive screening tool has shown promising performance when it comes to identifying children at risk of suffering obstructive sleep apnea syndrome. Moreover, it is ideal to be implemented in an outpatient consult in primary and secondary care.

Ejercicio físico como «medicina» en enfermedades crónicas durante la infancia y la adolescencia / Exercise as medicine in chronic diseases during childhood and adolescence

La actividad física (AF) y el ejercicio físico (EF) mejoran la calidad de vida global, previenen la aparición de enfermedades en niños y adolescentes sanos, y sirve para el tratamiento de enfermedades crónicas prevalentes en la infancia. Si la AF y el EF son medicina, el sedentarismo y la inactividad provocan enfermedad. Se revisa en este artículo la evidencia científica existente al respecto y se ponen al día las recomendaciones para los profesionales involucrados en la salud del niño, ya que es necesario un buen conocimiento de cómo prescribir EF y AF en pediatría en diferentes enfermedades. Las intervenciones para evitar la inactividad del niño y del adolescente deben estar sustentadas en el apropiado aumento del nivel de AF, mediante programas de integración y capacitación, que consigan una mejora conjunta de la condición física neuromuscular y del rendimiento físico, cognitivo y psicosocial. La Asociación Española de Pediatría, a través del Comité de Promoción de la Salud, propone estrategias que faciliten este objetivo para mejorar la salud de nuestros pacientes a través de la práctica de EF y el aumento de la AF

Physical activity (PA) and exercise improve the overall quality of life, as well as prevent the onset of diseases in healthy children and adolescents, and as an aid to treat prevalent chronic diseases in childhood. PA and exercise are like medicine, but sedentary lifestyle and inactivity cause disease. In this article, the existing scientific evidence in this field is reviewed and recommendations for professionals involved in child health are updated. A good knowledge of how to prescribe exercise and PA in paediatrics in different diseases is necessary. Interventions to avoid inactivity of children and adolescents must be supported by the appropriate increase in the level of PA, through integration and training programs, which achieve both an overall improvement of the neuromuscular physical condition and also physical, cognitive, and psychosocial performance. The Health Promotion Committee of Spanish Paediatric Association proposes strategies that help to obtain this objective, aiming to improve the health of our patients through the practice of exercise and the increase in PA

[Exercise as medicine in chronic diseases during childhood and adolescence]. / Ejercicio físico como «medicina¼ en enfermedades crónicas durante la infancia y la adolescencia.

Physical activity (PA) and exercise improve the overall quality of life, as well as prevent the onset of diseases in healthy children and adolescents, and as an aid to treat prevalent chronic diseases in childhood. PA and exercise are like medicine, but sedentary lifestyle and inactivity cause disease. In this article, the existing scientific evidence in this field is reviewed and recommendations for professionals involved in child health are updated. A good knowledge of how to prescribe exercise and PA in paediatrics in different diseases is necessary. Interventions to avoid inactivity of children and adolescents must be supported by the appropriate increase in the level of PA, through integration and training programs, which achieve both an overall improvement of the neuromuscular physical condition and also physical, cognitive, and psychosocial performance. The Health Promotion Committee of Spanish Paediatric Association proposes strategies that help to obtain this objective, aiming to improve the health of our patients through the practice of exercise and the increase in PA.

Identifying poor cardiorespiratory fitness in overweight and obese children and adolescents by using heart rate variability analysis under resting conditions.

Background: Childhood obesity, including overweight, continues increasing worldwide affecting health expectancy, quality of life and healthcare expenditure. These subjects have higher probability of suffering or developing cardio metabolic risk factors. Recent studies have revealed cardiorespiratory fitness (CRF) as a valuable clinical parameter to identify these subjects and have even suggested cut-off values. However, evaluating CRF in overweight and obese youth can be difficult to implement, unfriendly and expensive.Objective: Develop a screening tool to identify high-risk subjects in a representative population of those attending overweight/obesity assessment programmes without prior intervention. It will be based on heart rate variability parameters, which has strong association with CRF and cardio metabolic risk factors.Methods: Sixty-three subjects, overweight and obese, between 9 and 17 years of age, and of both sexes were enrolled. None of them had secondary obesity syndromes and/or suffered from acute or chronic disease. Anthropometric parameters, electrocardiogram signal recording under resting conditions and cardiorespiratory fitness - evaluated by oxygen consumption and time elapsed of cardiopulmonary exercise test - were measured.Results: Significant differences in the sympathetic nervous system activity - assessed by heart rate variability analysis - are observed when grouping by overweight and obesity degree as well as by CRF (poor/normal). Body mass index, puberty and sympathetic nervous system activity are the significant variables of a logistic regression model develop to identify poor CRF individuals. Its accuracy reaches 92%.Conclusions: A screening tool based on heart rate variability and anthropometric parameters was developed to identify subjects with higher probability of suffering or developing cardio metabolic risk factors.

Blood cell transcript levels in 5-year-old children as potential markers of breastfeeding effects in those small for gestational age at birth.

BACKGROUND: Nutrition of the newborn during the early postnatal period seems to be of capital importance and there is clinical evidence showing the protective effect of breastfeeding compared with formula feeding on childhood obesity and its comorbidities. Infants born small for gestation age may be more sensitive to the type of feeding during lactation. Here, we aimed to analyze the impact of birth weight and the type of infant feeding on the expression levels in peripheral blood cells of selected candidate genes involved in energy homeostasis in 5-year-old children, to find out potential early biomarkers of metabolic programming effects during this period of metabolic plasticity. METHODS: Forty subjects were recruited at birth and divided in four groups according to birth weight (adequate or small for gestational age) and type of infant feeding (breastfeeding or formula feeding). They were followed from birth to the age of 5 years. RESULTS: At 5 years, no significant differences regarding anthropometric parameters were found between groups, and all children had normal biochemical values. Expression levels of UCP2 and MC4R in peripheral blood cells were lower and higher, respectively, in formula feeding children compared with breastfeeding ones (P = 0.002 and P = 0.064, two-way ANOVA). Differences were more marked and significant by Student's t test in small for gestation age children (P < 0.001 and P = 0.017, respectively). Transcript levels of FASN and FTO in peripheral blood cells were also different according to the type of infant feeding, but only in small for gestation age children. CONCLUSIONS: Altogether, these results suggest that small for gestation age infants are more sensitive to the type of feeding during lactation, and transcript levels of particular genes in peripheral blood cells, especially the MC4R/UCP2 mRNA ratio, may precisely reflect these effects in the absence of clear differences in phenotypic traits.

Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes.

BACKGROUND: Early life is a period of drastic epigenetic remodeling in which the epigenome is especially sensitive to extrinsic and intrinsic influence. However, the epigenome-wide dynamics of the DNA methylation changes that occur during this period have not been sufficiently characterized in longitudinal studies. METHODS: To this end, we studied the DNA methylation status of more than 750,000 CpG sites using Illumina MethylationEPIC arrays on 33 paired blood samples from 11 subjects at birth and at 5 and 10 years of age, then characterized the chromatin context associated with these loci by integrating our data with histone, chromatin-state and enhancer-element external datasets, and, finally, validated our results through bisulfite pyrosequencing in two independent longitudinal cohorts of 18 additional subjects. RESULTS: We found abundant DNA methylation changes (110,726 CpG sites) during the first lustrum of life, while far fewer alterations were observed in the subsequent 5 years (460 CpG sites). However, our analysis revealed persistent DNA methylation changes at 240 CpG sites, indicating that there are genomic locations of considerable epigenetic change beyond immediate birth. The chromatin context of hypermethylation changes was associated with repressive genomic locations and genes with developmental and cell signaling functions, while hypomethylation changes were linked to enhancer regions and genes with immunological and mRNA and protein metabolism functions. Significantly, our results show that genes that suffer simultaneous hyper- and hypomethylation are functionally distinct from exclusively hyper- or hypomethylated genes, and that enhancer-associated methylation is different in hyper- and hypomethylation scenarios, with hypomethylation being more associated to epigenetic changes at blood tissue-specific enhancer elements. CONCLUSIONS: These data show that epigenetic remodeling is dramatically reduced after the first 5 years of life. However, there are certain loci which continue to manifest DNA methylation changes, pointing towards a possible functionality beyond early development. Furthermore, our results deepen the understanding of the genomic context associated to hyper- or hypomethylation alterations during time, suggesting that hypomethylation of blood tissue-specific enhancer elements could be of importance in the establishment of functional states in blood tissue during early-life.

Uric acid is linked to cardiometabolic risk factors in overweight and obese youths.

OBJECTIVE: Observational studies have indicated that high levels of serum uric acid are associated with the risk of cardiovascular disease. The aim of the present study is to investigate the association of uric acid with individual cardiometabolic risk factors, as well as their degree of clustering, in overweight and moderate obese youth. METHODS: Three hundred and thirty-three Caucasians of both sexes (149 women), from 5-18 years of age from those who underwent an assessment of overweight/obesity. Anthropometric parameters, office and 24-h blood pressure measurements and metabolic profile, including HDL-cholesterol, triglycerides, insulin, HOMA index and uric acid were assessed. RESULTS: Uric acid was significantly higher in boys than in girls. A positive significant association between uric acid, and office, daytime and night-time SBP, insulin and triglycerides was observed. When boys and girls were grouped by sex-specific uric acid tertiles, a progressive increment was observed in BMI, BMI z-score and waist circumference as well as fasting insulin and HOMA index. In boys, this was also present in office and ambulatory SBP. Likewise, the number of abnormal metabolic risk factors also increases with the uric acid values and the higher the number of metabolic components the higher the uric acid values. Moreover, in a multiple regression analysis, uric acid was significantly related with male sex, waist circumference, both office and night-time SBP and birth weight. CONCLUSION: The present study found a positive association between uric acid and blood pressure, insulin and triglycerides. As uric acid levels increase there is a relevant clustering of metabolic risk factors, whereas elevated blood pressure is the risk factor less frequently present. Further studies need to assess the mechanistic link between uric acid and the cardiometabolic risk factors.

Home-exercise Childhood Obesity Intervention: A Randomized Clinical Trial Comparing Print Versus Web-based (Move It) Platforms.

PURPOSE: To compare the impact of adhering to a Mediterranean diet plus mixed physical exercise program (Move-It) implemented by means of printed instructions or via a web-platform (with or without e-mail support) on body composition, physical fitness, and blood pressure. DESIGN AND METHODS: Randomized clinical trial. Fifty-two overweight or obese Spanish children and adolescents were randomly assigned to the print-based (n = 18), Move-It (n = 18), or Move-It plus support (n = 16) intervention groups. Two-way mixed ANOVA tests were used to compare any changes between the groups in terms of percentage body fat, physical fitness (VO2peak), handgrip strength, and systolic and diastolic blood pressure. The measurements were taken before and after a three-month mixed-exercise (aerobic and resistance) and Mediterranean-diet program which was either implemented by means of printed instructions or via a web-platform (with or without e-mail support). RESULTS: No statistical differences were found between groups. However, the results highlighted significant improvements in body fat percentage metrics over time for all three groups (print-based: -1.8%, 95%CI -3.3% to -0.3%; Move-It: -1.8%, 95%CI -3.3% to -0.3%; Move-It plus support: -2.0%, 95%CI -3.7% to -0.4%, P < 0.05). We also observed a tendency towards improvement in the VO2peak, handgrip strength, and blood pressure variable values 10 min after the exercise-stress test in these three groups. CONCLUSIONS: The program improved the body composition, regardless of the way it is implemented. PRACTICE IMPLICATIONS: A mixed physical exercise program lasting for three months, combined with a Mediterranean diet, improves the body composition of children and adolescents with overweight/obesity.

Relationship between body composition and postural control in prepubertal overweight/obese children: A cross-sectional study.

BACKGROUND: Excess body weight during childhood causes reduced motor functionality and problems in postural control, a negative influence which has been reported in the literature. Nevertheless, no information regarding the effect of body composition on the postural control of overweight and obese children is available. The objective of this study was therefore to establish these relationships. METHODS: A cross-sectional design was used to establish relationships between body composition and postural control variables obtained in bipedal eyes-open and eyes-closed conditions in twenty-two children. Centre of pressure signals were analysed in the temporal and frequency domains. Pearson correlations were applied to establish relationships between variables. Principal component analysis was applied to the body composition variables to avoid potential multicollinearity in the regression models. These principal components were used to perform a multiple linear regression analysis, from which regression models were obtained to predict postural control. FINDINGS: Height and leg mass were the body composition variables that showed the highest correlation with postural control. Multiple regression models were also obtained and several of these models showed a higher correlation coefficient in predicting postural control than simple correlations. These models revealed that leg and trunk mass were good predictors of postural control. More equations were found in the eyes-open than eyes-closed condition. INTERPRETATION: Body weight and height are negatively correlated with postural control. However, leg and trunk mass are better postural control predictors than arm or body mass. Finally, body composition variables are more useful in predicting postural control when the eyes are open.

Changes in physical fitness of a home-based physical exercise program in childhood obesity: A quasi-experimental uncontrolled study.

Few studies have evaluated the changes in physical fitness (PF) of obese children and adolescents of a physical activity program for the treatment of obesity, and even fewer have explored the modality of home-based physical exercise. The objective of this study is to evaluate the changes in PF and body composition (BC) of a home-based physical exercise for treating childhood obesity. Thirty-three overweight/obese children and adolescents participated for six months in a home-based intervention that combined aerobics and muscular strength exercises. The results were compared, before and after the intervention, for the different PF components (VO2max, abdominal muscle resistance strength, and lower body explosive strength) and BC (body mass index Z-score (BMI-Z), percentage of body fat, and fat-free mass) variables. A significant reduction was observed in the percentage of body fat (4.7%) and the BMI- Z score (.23), and there was an increase in the fat-free mass of 2.9 kg ( p < .001). In addition, the VO2max showed a significant increase ( p < .05). The results of the different strength tests also showed significant improvements ( p < .05). Our findings support the effectiveness of this program improving not only BC but also PF. However, our results should be interpreted with caution due to lack of control group.

Sympathetic neural activity, metabolic parameters and cardiorespiratory fitness in obese youths.

OBJECTIVE: The main objective of this cross-sectional study is to assess the cardiac autonomic neural activity in the presence of abnormally increased body weight in youths and its relationship to metabolic risk factors and cardiorespiratory fitness (CRF). METHODS: Sixty-four overweight and obese patients, aged 9-17 years, of both sexes, stratified according to the international BMI cut-off, were enrolled. Continuous ECG was recorded during 15 min in resting conditions, and the heart rate variability (HRV) was measured in the time domain, frequency domain and for nonlinear dynamics. In addition, cardiometabolic risk factors and CRF in effort conditions were assessed. RESULTS: Among the overweight and obese youths, no significant differences were observed regarding metabolic parameters and heart rate, although CRF was the lowest in the severely obese youths. Likewise, no significant differences were observed in HRV, independent of how it was assessed. A positive and significant relationship, independent of the degree of obesity, pubertal stage and breathing rate under resting conditions, has been observed among sympathovagal balance, insulin and the homeostatic model assessment index. Furthermore, CRF assessed by volume oxygen peak was associated with insulin levels (r = -0.273; P < 0.05), the SD of the NN interval series (r = 0.268, P < 0.05) and the long-term variation using the Poincaré plot (PS1: r = 0.275, P < 0.05; PS2: r = 0.273, P < 0.05). CONCLUSION: The key findings of the present study were the presence of a link among fasting insulin, HRV and CRF independent of the degree of obesity, indicating the heterogeneity of obese children and adolescents.

Longitudinal study of DNA methylation during the first 5 years of life.

BACKGROUND: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. METHODS: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina(®) Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. RESULTS: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. CONCLUSIONS: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention.