Lean Children Research Articles

Early changes in adipokines from overweight to obesity in children and adolescents

ObjectiveChildhood obesity has been associated with metabolic syndrome and cardiovascular diseases. This study aimed to compare plasma levels of traditional metabolic markers, adipokines and soluble tumor necrosis factor receptor type 1 (sTNFR1) in overweight, obese and lean children. We also assessed the relationships of these molecules with classical metabolic risk factors. MethodsThis study included 104 children and adolescents, which were grouped as: lean (n=24), overweight (n=30), and obese subjects (n=50). They were subjected to anthropometrical, clinical and laboratorial measurements. All measurements were compared between groups. Correlation analyses were also performed to evaluate the association between clinical data, traditional metabolic markers, adipokines and sTNFR1. ResultsFasting glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), LDL-cholesterol and triglycerides were comparable in lean, overweight and obese subjects. Plasma levels of sTNFR1 were similar in lean and overweight subjects, but significantly increased in obese group. Leptin, adiponectin and resistin levels did not differ when overweight were compared to obese subjects. However, all adipokines differed significantly when lean subjects were compared to overweight and obese individuals. Plasma levels of adiponectin were negatively correlated with body mass index (BMI), whereas leptin, resistin and sTNFR1 concentrations positively correlated with BMI. ConclusionOur results showed significant differences in circulating levels of the evaluated markers when lean, overweight and obese individuals were compared, suggesting that these biomarkers may change from lean to overweight and from overweight to obesity.

Betatrophin: no relation to glucose metabolism or weight status in obese children before and after lifestyle intervention.

The influences of obesity, glucose metabolism, gender, and puberty on betatrophin levels and the longitudinal relationships between weight loss, metabolic changes and betatrophin have not yet been studied in childhood. Cross-sectional and longitudinal analysis of weight status (standard deviation score-body mass index (SDS-BMI)), homeostasis model assessment insulin resistance (HOMA-IR), gender, and pubertal stage were evaluated in 69 obese children (51% female, age 11.9 ± 2.0 years) participating in lifestyle intervention over a 1-year period. An oral glucose tolerance test was performed in 53 of the 69 children. Twenty normal weight children (50% female, age 12.3 ± 3.0 years) served as controls. Circulating betatrophin did not differ significantly between obese and lean children (1.99 ± 0.90 vs 2.35 ± 0.28, mean ± SD, P = .155). At baseline, betatrophin did not differ in obese patients with vs without glucose intolerance (1.89 ± 0.96 vs 2.031 ± 0.91 ng/mL; P = .591) and obese with (delta SDS-BMI >0.4) vs without successful obesity intervention (1.89 ± 0.94 vs. 2.07 ± 0.87 ng/mL; P = 0.396). In multiple linear regression analyses, pubertal stage was associated with betatrophin (b: 0.48, P = .027), while gender, age, BMI, blood pressure, fasting glucose, HOMA-IR, triglycerides, LDL- and HDL-cholesterol were not related to betatrophin at baseline. At the end of the 1-year intervention, changes of betatrophin were not significantly associated with any parameter after controlling for multiple covariates including age and changes of pubertal stages. Our data do not support a relationship between betatrophin and weight status or glucose tolerance, insulin resistance, and lipid metabolism in children.

Gender Differences in the Alteration of Obesogenic Environments in Korean Children According to GNB3 Polymorphism

Background: A single-nucleotide polymorphism, C825T in the G protein β3 subunit (GNB3) gene, is associated with essential hypertension and obesity. However, the potential interaction of the GNB3C825T polymorphism with obesogenic environmentsin obesity of Korean children has not been closely evaluated yet. Methods: We analyzed data collected from 635 boys and 627 girls aged 8-9 yearsrecruited from seven elementary schools in Seoul, South Korea. Measures of anthropometry and blood pressure (BP) as well as fasting blood samples were used in the analysis. Three-day food records were collected. Results: Obese children had higher BP, lipid profiles and insulinresistance-related factors than did lean children. Higher body mass index (BMI), waist circumference (WC)and BP and lowerplasma lipid profiles were observed in boys than in girls. The genotype frequencies of the GNB3 polymorphism were CC=23.7%, CT=52.1%, and TT=24.2%, and the allele frequencies were C allele=49.7% and T allele=50.3 in the subjects. There was no significant difference according to gender and obesity with allelic frequencies. Boys with the T allele were more obese thanthose with the C allele, but the C and T alleles, according to anthropometrics and plasma variables, did not differ between the obesity and lean groups. In contrast to boys, obese girls with the T allele had lower BMI and WC than those with the C allele, although they had higher plasma cholesteroland energy intakes compared to those with the C allele. We found that the HDL3c subtype, fasting insulin and homeostasis model assessment of insulin resistance decreased with increasing HDL peak amount, which was positively correlated with total HDLcholesterol. However, the HDL subtypes were not changed by the GNB3 C825T polymorphism. Conclusion: The GNB3 C825T polymorphism influences the childhood obesity rate and energy intakesdifferentially by gender in Korean children.

Urinary markers of nucleic acid oxidation in Danish overweight/obese children and youths

Urinary excretion of the RNA and DNA oxidation markers, 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in newly diagnosed adult type 2 diabetics are reported to be long-term predictors of mortality independent of conventional risk factors. In the current study, we investigated the relationships between urinary markers of nucleic acid oxidation concentrations and the degree of obesity and glucose metabolism in overweight compared to lean children. Forty-two (24 girls) overweight and 35 lean (19 girls) children and adolescents were recruited from the Registry of the Danish Childhood Obesity Biobank. Anthropometric measurements were collected at baseline and glucose metabolism was assessed by an oral glucose tolerance test. A urine sample was obtained during the test. Linear regression did not demonstrate any associations between the urinary markers and the degree of obesity or glucose metabolism in lean and obese children. However, sub-analyses adjusted for age, sex, and the degree of obesity showed positive associations between the 2 h glucose and the urinary markers, 8-oxoGuo (p = 0.02, r2= 0.63) and 8-oxodG (p = 0.046, r2= 0.48), and between the insulinogenic index and 8-oxoGuo (p = 0.03, r2 = 0.60) in the 12 obese children exhibiting impaired glucose tolerance. Excretion of the urinary markers of nucleic acid oxidation and the degree of obesity or the glucose metabolism were not associated in this study. Nevertheless, obese children with impaired glucose tolerance seem to exhibiting an increased oxidative stress level, but due to the small sample size in this study, further investigations are required to elucidate this correlation.

Initial hyperinsulinemia and subsequent β-cell dysfunction is associated with elevated palmitate levels.

The prevalence of obesity-related diabetes in childhood is increasing and circulating levels of nonesterified fatty acids may constitute a link. Here, the association between palmitate and insulin secretion was investigated in vivo and in vitro. Obese and lean children and adolescents (n = 80) were included. Palmitate was measured at fasting; insulin and glucose during an oral glucose tolerance test (OGTT). Human islets were cultured for 0 to 7 d in presence of 0.5 mmol/l palmitate. Glucose-stimulated insulin secretion (GSIS), insulin content and apoptosis were measured. Obese subjects had fasting palmitate levels between 0.10 and 0.33 mmol/l, with higher average levels compared to lean subjects. While obese children with elevated palmitate (>0.20 mmol/l) had accentuated insulin levels during OGTT, obese adolescents with high palmitate had delayed first-phase insulin response. In human islets exposed to palmitate for 2 d GSIS was twofold enhanced, but after 7 d attenuated. Intracellular insulin content decreased time-dependently in islets cultured in the presence of palmitate and cleaved caspase 3 increased. The rapid accentuated and delayed insulin secretory responses observed in obese children and adolescents, respectively, with high palmitate levels may reflect changes in islet secretory activity and integrity induced by extended exposure to the fatty acid.

Impact of Obesity on Clinical Outcomes in Urban Children Hospitalized for Status Asthmaticus.

The prevalence of both childhood asthma and obesity remain at historically high levels and disproportionately affect urban children. Asthma is a common and costly cause for pediatric hospitalization. Our objective was to determine the effect of obesity on outcomes among urban children hospitalized with status asthmaticus. A retrospective cohort study was performed by using billing system data and chart review to evaluate urban children admitted for asthma. Demographics, asthma severity, reported comorbidities, and outcomes were assessed. Obesity was defined by BMI percentile (lean<85%, overweight 85%-95%, obese≥95%). Outcomes were length of stay, hospitalization charges, ICU stay, repeat admissions, and subsequent emergency department (ED) visits. Bivariate analysis assessed for differences between overweight/obese and lean children. Multivariable regression assessed the relationship between overweight status and primary outcomes while controlling for other variables. Post hoc age-stratified analysis was also performed. The study included 333 subjects; 38% were overweight/obese. Overweight/obese children admitted with asthma were more likely than lean children to have subsequent ED visits (odds ratio 1.6, 95% confidence interval 1.0-2.6). When stratified by age, overweight/obese preschool-age children (<5 years) were >2 times as likely to have repeat ED visits than lean preschool-age children (odds ratio 2.3, 95% confidence interval 1.0-5.6). There were no differences in the other outcomes between overweight/obese and lean individuals within the entire cohort or within other age groups.

Energy Expenditure in Children with Prader‐Willi Syndrome During Walking

Prader‐Willi Syndrome (PWS) is a complex genetic disorder caused by a deletion of the paternal chromosome 15. PWS is characterized by increased body fat, hypotonia, growth hormone (GH) deficiency, motor and cognitive disabilities, and hyperphagia, potentially resulting in obesity. This study measured and compared calorie expenditure while walking in PWS and controls. Participants included 8 children with PWS (7 were on GH replacement therapy; mean age = 11.1±0.8 y; body mass = 44.7±11.7 kg; body fat = 37.2±11.4 %; lean mass = 26.4±4.3 kg), 9 lean children (mean age = 9.8±2.0y; body mass = 35.4±11.3 kg; body fat = 22.2±8.6 %; lean mass = 25.5±11.6 kg), and 10 obese children (mean age = 10.6±1.1 y; body mass = 62.1±14.6 kg; body fat = 44.4±3.7 %; lean mass = 33.3±5.1 kg). Fat free mass (FFM) and body fat % were measured with dual x‐ray absorptiometry (DXA). Participants walked for three 5‐minute bouts on a treadmill at 2.0, 2.5, and 3.0 mph, with a 6‐minute seated rest period in between speeds. Expired gases were analyzed for minutes 4–5 of each speed. There were no group by time interactions for any of the variables of interest. PWS children had a higher VO2 ml/kg/min than obese children (p=0.04), but were similar to lean children (p=1.00); PWS children exhibited a greater caloric expenditure in kcal/kg/min than obese (p=0.03), but similar to lean (p=1.00). No other differences were found among the PWS and control groups during walking for VO2 when expressed in L/min or ml/FFM/min, caloric expenditure when expressed in kcal/min or kcal/FFM/min, or metabolic equivalents. The results of this study suggest that children with PWS are expending similar calories as lean controls of comparable body mass while walking. Thus, the difference in body fat does not appear to affect calories spent doing the same absolute work in PWS.

Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution?

BackgroundObese children for unknown reasons report greater asthma symptoms. Asthma and obesity both independently associate with gastro-oesophageal reflux symptoms (GORS). Determining if obesity affects the link between GORS and asthma...

Obesity and Prader-Willi Syndrome Affect Heart Rate Recovery from Dynamic Resistance Exercise in Youth.

Following exercise, heart rate decline is initially driven by parasympathetic reactivation and later by sympathetic withdrawal. Obesity delays endurance exercise heart rate recovery (HRR) in both children and adults. Young people with Prader-Willi Syndrome (PWS), a congenital cause for obesity, have shown a slower 60-s endurance exercise HRR compared to lean and obese children, suggesting compromised regulation. This study further evaluated effects of obesity and PWS on resistance exercise HRR at 30 and 60 s in children. PWS (8–18 years) and lean and obese controls (8–11 years) completed a weighted step-up protocol (six sets x 10 reps per leg, separated by one-minute rest), standardized using participant stature and lean body mass. HRR was evaluated by calculated HRR value (HRRV = difference between HR at test termination and 30 (HRRV30) and 60 (HRRV60) s post-exercise). PWS and obese had a smaller HRRV30 than lean (p < 0.01 for both). Additionally, PWS had a smaller HRRV60 than lean and obese (p = 0.01 for both). Obesity appears to delay early parasympathetic reactivation, which occurs within 30 s following resistance exercise. However, the continued HRR delay at 60 s in PWS may be explained by either blunted parasympathetic nervous system reactivation, delayed sympathetic withdrawal and/or poor cardiovascular fitness.

Effects of resistance training on cardiovascular health in non-obese active adolescents

To determine the benefits of a 10-wk resistance training programme on cardiovascular health in non-obese and active adolescents. This is a pragmatic randomised controlled intervention. The study was carried out in a Hong Kong Government secondary school. Thirty-eight lean and active boys and girls were randomised to either the resistance training group or the control group. Students in the resistance training group received in-school 10-wk supervised resistance training twice per week, with each session lasting 70 min. Main outcome measures taken before and after training included brachial endothelial dependent flow-mediated dilation, body composition, fasting serum lipids, fasting glucose and insulin, high sensitive C-reactive protein, 24-h ambulatory blood pressure and aerobic fitness. The only training related change was in endothelial dependent flow-mediated dilation which increased from 8.5% to 9.8%. A main effect of time and an interaction (P < 0.005) indicated that this improvement was a result of the 10-wk resistance training. Main effects for time (P < 0.05) in a number of anthropometric, metabolic and vascular variables were noted; however, there were no significant interactions indicating the change was more likely an outcome of normal growth and development as opposed to a training effect. Ten weeks of resistance training in school appears to have some vascular benefit in active, lean children.

Expression of candidate genes associated with obesity in peripheral white blood cells of Mexican children.

IntroductionObesity is a chronic, complex, and multifactorial disease, characterized by excess body fat. Diverse studies of the human genome have led to the identification of susceptibility genes that contribute to obesity. However, relatively few studies have addressed specifically the association between the level of expression of these genes and obesity.Material and methodsWe studied 160 healthy and obese unrelated Mexican children aged 6 to 14 years. We measured the transcriptional expression of 20 genes associated with obesity, in addition to the biochemical parameters, in peripheral white blood cells. The detection of mRNA levels was performed using the OpenArray Real-Time PCR System (Applied Biosystems).ResultsObese children exhibited higher values of fasting glucose (p = 0.034), fasting insulin (p = 0.004), low-density lipoprotein (p = 0.006), triglycerides (p < 0.001), systolic blood pressure and diastolic blood pressure (p < 0.001), and lower values of high-density lipoprotein (p < 0.001) compared to lean children. Analysis of transcriptional expression data showed a difference for ADRB1 (p = 0.0297), ADIPOR1 (p = 0.0317), GHRL (p = 0.0060) and FTO (p = 0.0348) genes.ConclusionsOur results suggest that changes in the expression level of the studied genes are involved in biological processes implicated in the development of childhood obesity. Our study contributes new perspectives for a better understanding of biological processes involved in obesity. The protocol was approved by the National Committee and Ethical Committee Board from the Mexican Social Security Institute (IMSS) (IMSS FIS/IMSS/PRIO/10/011).

Association between serum soluble tumor necrosis factor-α receptors and early childhood obesity.

This study aimed to characterize the inflammatory cytokine profiles and further validate the significantly different cytokines in the serum obtained from obese children aged 36-48 months. Four obese children and four lean controls were randomly selected for inflammatory cytokine array assay, in which two cytokines [soluble tumor necrosis factor-α receptors (sTNFRs) 1 and 2] were found to be significantly different. Both cytokines (sTNFR1 and sTNFR2) were then further validated through enzyme-linked immunosorbent assay (ELISA) in 61 obese children and 52 lean children. ELISA results revealed that serum sTNFR1 level in obese children significantly increased (p = 0.003), whereas sTNFR2 did not change significantly (p = 0.069). Stratified analysis by gender showed that only obese girls presented increased sTNFR1 (p = 0.005) and sTNFR2 (p = 0.049) levels. We conclude that serum sTNFR1 is elevated in early childhood obesity. Moreover, serum sTNFR1 and sTNFR2 are associated with obese girls but not obese boys, thereby suggesting that serum sTNFRs in early childhood obesity may be sex related.

Correlation between body mass index and faecal microbiota from children

Childhood obesity is an increasing problem at the global level and considered as a risk factor for obesity development and the associated co-morbidities in adult life. In this study, the occurrence of Bacteroides fragilis group, Clostridium spp., Bifidobacterium spp. and Escherichia coli in 84 faecal samples from 30 obese, 24 overweight and 30 lean children was verified by culture technique and quantitative determination by quantitative PCR. In addition, Lactobacillus spp. and Methanobrevibacter smithii were also analysed. A correlation between the body mass index (BMI) and these bacteria was sought. Bacteroides vulgatus, Clostridium perfringens and Bifidobacterium adolescentis were most prevalent in all samples evaluated by culture-method. The B. fragilis group were found at high concentrations in obese and overweight children when compared with the lean ones (p 0.015). The obese and overweight children harboured higher numbers of Lactobacillus spp. than lean children (p 0.022). The faecal concentrations of the B. fragilis group (r = 0.24; p 0.026) and Lactobacillus spp. (r = 0.44; p 0.002) were positively correlated with BMI. Bifidobacterium spp. were found in higher numbers in the lean group than the overweight and obese ones (p 0.042). Furthermore, a negative correlation between BMI and Bifidobacterium spp. copy number (r = −0.22; p 0.039) was observed. Our findings show some difference in the intestinal microbial ecosystem of obese children compared with the lean ones and a significant association between number of Lactobacillus spp. and B. fragilis group and BMI.

Oral Fat Sensing and CD36 Gene Polymorphism in Algerian Lean and Obese Teenagers.

Growing number of evidences have suggested that oral fat sensing, mediated by a glycoprotein CD36 (cluster of differentiation 36), plays a significant role in the development of obesity. Indeed, a decreased expression of CD36 in some obese subjects is associated with high dietary fat intake. In the present study, we examined whether an increase in body mass index (BMI) is associated with altered oleic acid lingual detection thresholds and blood lipid profile in young Algerian teenagers (n = 165). The obese teenagers (n = 83; 14.01 ± 0.19 years; BMI z-score 2.67 ± 0.29) exhibited higher lingual detection threshold for oleic acid than lean participants (n = 82, 13.92 ± 0.23 years; BMI z-score 0.03 ± 0.0001). We also studied the association between rs1761667 polymorphism of CD36 gene and obesity. The AA and AG genotypes were more frequent in obese teenagers, whereas GG genotype was more common in lean participants. The A-allele frequency was higher in obese teenagers than that in lean children. We report that rs1761667 polymorphism of CD36 gene and oro-gustatory thresholds for fat might play a significant role in the development of obesity in young teenagers.

Abstract CN10-03: Childhood obesity and leukemia: Opportunities for intervention

Abstract Obesity is a major contributor to cancer mortality, and is responsible for ~90,000 cancer deaths per year in the U.S. Part of this association can be attributed to the effect of obesity to increase cancer incidence, while obesity has been shown to worsen the outcome from a number of types of cancer. Retrospective studies have shown that obese children diagnosed with the high-risk form of the most common childhood cancer, acute lymphoblastic leukemia (HR-ALL) have a substantially higher risk of relapse than lean children. We have investigated these associations, generating laboratory models to investigate how obesity might impact ALL progression and treatment. Using two mouse models, we found that obesity accelerates the appearance of spontaneous leukemia. We have further discovered that obese mice implanted with leukemia had poorer survival after treatment with either vincristine or L-asparaginase. We have identified several effects of adipocytes which appear to contribute to this worse outcome. Adipocytes attract ALL cells to migrate into adipose tissue via secretion of the chemokine CXCL12, protect ALL cells from a number of chemotherapies, absorb chemotherapy leading to unfavorable pharmacokinetics, and secrete glutamine and possibly other fuels to support leukemia cell proliferation. In all, adipocytes have a number of effects which likely contribute to the worse prognosis in obese patients with ALL. These effects are particularly concerning given the high prevalence of overweight and obesity in leukemia patients. Two-thirds of adults and one-third of children in the U.S. are either overweight or obese. Almost half of new patients with HR-ALL in our institution are overweight and obese. Furthermore, we have observed that the body fat of these patients increases by ~20% during the first month of treatment, and even further by several months into therapy. HR-ALL patients therefore have a large and increasing burden of adipose tissue which may directly impair leukemia treatment and worsen prognosis. We now have evidence that the effect of obesity might be reversible. A retrospective analysis of HR-ALL patients showed that those who were obese at diagnosis, but lost weight and became non-obese for more than half of their treatment, had an improved outcome, similar to patients who were never overweight or obese. Experiments in our laboratory demonstrated that switching obese mice to a low-fat diet at start of ALL treatment substantially improves outcome from vincristine treatment, compared to those continued on the high fat-diet (92% vs. 17% survival, p&amp;lt;0.001). In fact, this dietary intervention led to a better survival than even control mice raised on the same low-fat diet. These bench and clinical findings set the stage for an obesity-targeted intervention in children with ALL. We hypothesize that targeting obesity during leukemia treatment will reduce body fat gain, improve quality of life, and potentially improve outcome. Citation Format: Steven D. Mittelman. Childhood obesity and leukemia: Opportunities for intervention. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN10-03.

1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents.

ObjectivesThis cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children.MethodsFasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8–18 years.ResultsIn 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed.Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol.ConclusionHepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.

Influence of lifestyle on the FAIM2 promoter methylation between obese and lean children: a cohort study

目标 肥胖相关基因Fas细胞凋亡抑制分子2(FAIM2)可以被营养状况调控，并且其启动子甲基化水平与肥胖显著相关。生活行为因素，如静态生活行为和运动，可以修饰与肥胖相关的表观遗传状态。但是，FAIM2影响肥胖的分子机制是否与生活行为相关还不清楚。本研究检测了肥胖和消瘦儿童间FAIM2启动子甲基化水平与静态生活行为和运动的潜在差异。 设计 人群研究。 研究地点 首都儿科研究所。 研究对象 来自2013年北京8～18岁儿童横断面调查，包括59例肥胖儿童，并以39例消瘦儿童作为对照。 主要和次要结果测量 采用Sequenom MassARRAY平台对FAIM2启动子甲基化水平进行定量检测。采用问卷调查的方式收集了静态生活行为和运动数据。采用多重线性回归检测肥胖和消瘦儿童间不同生活行为方式对甲基化水平影响的差异。 结果 FAIM2启动子区域7个CpG位点的甲基化水平与静态生活行为显著相关。其中，位点–975、位点–413、位点–362/–360和位点–353/–349的P值分别是0.000 04、0.000 09、0.000 6和0.000 05。在运动水平小于150分钟/周的肥胖和消瘦病例间有4个CpG位点的甲基化水平存在差异。 结论 本研究首次证明，在肥胖和消瘦儿童间的FAIM2启动子甲基化水平与静态生活行为和运动的关系存在差异。本研究结果表明生活行为可能介导FAIM2参与肥胖的过程。

Cytokine Responses to Acute Intermittent Aerobic Exercise in Children With Prader-Willi Syndrome and Nonsyndromic Obesity.

Prader-Willi Syndrome (PWS), the best characterized form of syndromic obesity, presents with abnormally high fat mass. In children, obesity presents with low-grade systemic inflammation. This study evaluated if PWS and/or nonsyndromic obesity affected cytokine responses to intermittent aerobic exercise in children. Eleven children with PWS (11 ± 2 y, 45.4 ± 9.5% body fat), 12 children with obesity (OB) (9 ± 1 y, 39.9 ± 6.8% body fat), and 12 lean (LN) children (9 ± 1 y, 17.5 ± 4.6% body fat) participated. Children completed 10 2-min cycling bouts of vigorous intensity, separated by 1-min rest. Blood samples were collected preexercise (PRE), immediately postexercise (IP), and 15, 30, and 60 min into recovery to analyze possible changes in cytokines. In all groups, IL-6 and IL-8 concentrations were greater during recovery compared with PRE. PWS and OB exhibited higher IL-6 area under the curve (AUC) than LN (p < .01 for both). PWS demonstrated higher IL-8 AUC than LN (p < .04). IL-10, TNF-α, and IFN-γ did not change with exercise (p > .05 for all). Results indicate that children with PWS respond with increased Il-6 and IL-8 concentrations to acute exercise similarly to controls. Excess adiposity and epigenetic modifications may explain the greater integrated IL-6 and IL-8 responses in PWS compared with controls.

Internalizing and externalizing problems in obese children and adolescents: associations with daily salivary cortisol concentrations.

Pediatric obesity commonly co-exists with emotional and behavioral disorders, while disturbed cortisol concentrations have been reported in both obese and chronically stressed individuals with anxiety and/or depression. We investigated the prevalence of internalizing and externalizing problems, reported by both parents and children, in a clinical population of obese children (OC) compared to normal-weight children. We examined the role of cortisol as a potential mediator between obesity and such problems. We compared 110 obese with 31 normal-weight children. The Greek version of the child behavior checklist (CBCL) and the youth self-report (YSR) were used and salivary cortisol was determined serially five times a day. T-scores of internalizing problems (anxiety/depression, social withdrawal, somatic complains) reported by both children (49.3±12.3 vs. 43.2±9.1) and mothers (60.6±11.3 vs. 50.6±10.4) were significantly higher (p=0.03 and p<0.001, respectively) in the obese than in the lean children. Externalizing problems (delinquency, rule-breaking behaviors) reported only by mothers were significantly higher in the OC (57.2 ±10.5 vs. 48.2±13.3, p=0.003). The cortisol area under the curve (AUC) was significantly smaller (p=0.03) in the OC than in the controls; however, a cortisol correlation with internalizing/externalizing symptoms was not observed. There is a high prevalence of internalizing and externalizing problems in a clinical population of OC. A mediation effect of cortisol in the relation between internalizing/externalizing problems and obesity could not be supported.

Responses of Lipolysis to Physical Activity in Lean and Overweight Children

PURPOSE: This investigation was conducted to determine whether there were differences in lipolytic responses to physical activity between lean (LN) and overweight/obese (OW) children. METHODS: Fifty-four children (EX: 15 LN and 39 OW, age 8-11yr) performed 20 min of aerobic exercise eliciting an average heart rate of 140 beats/min with additional 6 min of warm-up and cool-down 2.5 hours following a standardized breakfast (∼300 kcal), while 22 children (CON: 9 LN and 13 OW, age 8-11 yr) remained rested following breakfast. Microdialysis probes were inserted into the subcutaneous abdominal adipose tissue to monitor interstitial glycerol (lipolysis) and microvascular blood flow. Three one-hour dialysate samples were collected with exercise performed in the second hour (or rest in CON). Two-way (time by intervention group) ANOVAs were separately performed in LN and OW. RESULTS: For interstitial glycerol concentrations in LN, significant effects were a time by intervention group interaction, and main effects for time and intervention group (p<0.05). Interstitial glycerol concentration increased (p<0.05) with exercise and decreased (p<0.05) after exercise in EX (176 ± 22 to 261 ±34 to 220 ± 36 uM), but remained unchanged in CON (114 ± 28 to 122 ± 44 to 119 ± 47 uM). In OW, no statistical difference was found in either interstitial glycerol concentration between EX and CON or over time (EX: 281 ± 30 to 326 ± 65 to 311 ± 35 uM; CON: 204 ± 52 to 254 ± 112 to 229 ± 61 uM). In LN, a time by intervention group interaction was found (p<0.05) in ethanol outflow/inflow (O/I, inversely related to microvascular blood flow). Ethanol O/I increased in EX (0.55 ± 0.04 to 0.64 ± 0.04 to 0.61 ± 0.04, p<0.05) while decreased in CON (0.62 ± 0.06 to 0.57 ± 0.05 to 0.52 ± 0.05, p<0.05). In OW, no statistical difference was found in either ethanol O/I between EX and CON or over time (EX: 0.76 ± 0.02 to 0.74 ± 0.03 to 0.73 ± 0.02; CON: 0.73 ± 0.03 to 0.71 ± 0.04 to 0.70 ± 0.04). CONCLUSIONS: Lipolytic response to acute aerobic exercise is lower in overweight compared to lean children. Greater lipolytic response during exercise in lean children was evident even with a decreased adipose tissue microvascular blood flow during exercise in lean children. Supported by NIH RO1DK071081.