Circulating levels of asprosin in children with obesity: a systematic review and meta-analysis.

BACKGROUND: Prior studies reported that elevated asprosin level was associated with obesity in adults and animal models. However, the relationship between asprosin level and children with obeisty remains controversial. The aim of our analysis was to systematically review available literatures linking asprosin and children with obesity for a comprehensive understanding of the relationship between circulating asprosin level and obesity in children. METHODS: Eight databases were gleaned for studies published up to January 2024. Standard mean difference with 95% confidence interval (CI) and Fisher's Z transformation was calculated to evaluate the relationship between asprosin level and children with obesity using the Review Manager 5.4 Software. Other indicators were measured via mean difference with 95% CI. RESULTS: Six observational studies were included both in systematic review and meta-analysis. The current evidence indicated that no significant difference was observed in the level of circulating asprosin between the children with and without obesity (SMD = 0.37; 95% CI:-0.22-0.95, p = 0.22). However, Fisher's Z transformation suggested the positive association of circulating asprosin levels and clinical index measuring the degree of obesity: total cholesterol (Fisher's Z: 0.11, 95% CI: 0.02-0.20, p = 0.02). CONCLUSIONS: Circulating asprosin level was not independently related to childhood obesity currently. More rigorous longitudinal researches were required to disentangle the causations. However, the positive association of asprosin levels and total cholesterol indicated that asprosin might get involved in the lipid-metabolism of childhood obesity, asprosin might be a prospective bio-index and targeted treatment of total cholesterol metabolism besides the role of glucogenic and orexigenic. TRIAL REGISTRATION: Prospero ID: CRD42023426476.

Waist-to-height ratio cut-off points to predict obesity in adolescents and association with inflammatory markers / Puntos de corte de la relación cintura-altura para predecir la obesidad en adolescentes y asociación con marcadores inflamatorios

Introduction: obesity increases inflammatory molecules and cardiovascular risk even in young populations. New indicators are being investigated, including the waist-to-height ratio (WHtR) to predict obesity and the relationship with inflammatory markers in childhood and adolescence. Objective: to identify the cut-off points of the WHtR to determine obesity and its association with inflammatory markers in adolescents in São Luís, state of Maranhão, Brazil. Methods: this is a cross-sectional study, with 2,209 adolescents aged 18 and 19, belonging to the third phase of the birth cohort entitled “RPS”, carried out in 2016. The total area under the ROC curve (AuC) was identified to assess the predictive capacity of WHtR in relation to body fat percentage (%BF), obtained by air displacement plethysmography (ADP). The association of WHtR with inflammatory markers interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and c-reactive protein (CRP) was evaluated. Results: prevalence of obesity by the %BF was 10.3 % in males and 40.4 % in females. The cut-off points for the WHtR were 0.50 for females and 0.51 for males, with an AuC of 0.90 (95 % CI: 0.88-0.92) and 0.93 (95 % CI: 0.90-0.97). There was an association of elevated WHtR with higher levels of IL-6 and CRP (p < 0.05). Conclusion: the predictive capacity of WHtR for obesity was excellent. Elevated values of the WHtR were associated with early inflammatory markers. This study contributed to the identification of cut-off points for simple and low-cost anthropometric indicators. (AU)

Introducción: la obesidad aumenta las moléculas inflamatorias y el riesgo cardiovascular incluso en poblaciones jóvenes. Se están investigando nuevos indicadores, incluida la relación cintura-altura (RCE) para predecir la obesidad y la relación con los marcadores inflamatorios en la infancia y la adolescencia. Objetivo: identificar los puntos de corte de la RCE para determinar la obesidad y su asociación con marcadores inflamatorios en adolescentes de São Luís, estado de Maranhão, Brasil. Métodos: se trata de un estudio transversal con 2.209 adolescentes de 18 y 19 años pertenecientes a la tercera etapa de la cohorte de nacimiento denominada “RPS”, realizado en 2016. Se identificó el área total bajo la curva ROC (AuC) para evaluar la capacidad predictiva del RCE en relación al porcentaje de grasa corporal (%GC), obtenido a través del pletismografía por desplazamiento de aire (PDA). Se evaluó la asociación de la RCE con los marcadores inflamatorios interleucina-6 (IL-6), factor de necrosis tumoral (TNF-α) y proteína C reactiva (PCR). Resultados: se halló una prevalencia de obesidad por %GC del 10,3 % en hombres y 40,4 % en mujeres. Los puntos de corte para la RCE fueron 0,50 para mujeres y 0,51 para hombres, con un AuC de 0,90 (IC 95 %: 0,88-0,92) y 0,93 (IC 95 %: 0,90-0,97). Hubo una asociación de RCE de nivel superior con niveles más altos de IL-6 y PCR (p < 0,05). Conclusión: la capacidad de predicción de la RCE para la obesidad fue excelente y los valores elevados de RCE se asociaron con marcadores inflamatorios tempranos. Este estudio contribuyó a la identificación de puntos de corte para indicadores antropométricos simples y de bajo coste. (AU)

Waist-to-height ratio cut-off points to predict obesity in adolescents and associa-tion with inflammatory markers.

Introduction: Introduction: obesity increases inflammatory molecules and cardiovascular risk even in young populations. New indicators are being investigated, including the waist-to-height ratio (WHtR) to predict obesity and the relationship with inflammatory markers in childhood and adolescence. Objective: to identify the cut-off points of the WHtR to determine obesity and its association with inflammatory markers in adolescents in São Luís, state of Maranhão, Brazil. Methods: this is a cross-sectional study, with 2,209 adolescents aged 18 and 19, belonging to the third phase of the birth cohort entitled "RPS", carried out in 2016. The total area under the ROC curve (AUC) was identified to assess the predictive capacity of WHtR in relation to body fat percentage (%BF), obtained by air displacement plethysmography (ADP). The association of WHtR with inflammatory markers interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and c-reactive protein (CRP) was evaluated. Results: prevalence of obesity by the %BF was 10.3 % in males and 40.4 % in females. The cut-off points for the WHtR were 0.50 for females and 0.51 for males, with an AUC of 0.90 (95 % CI: 0.88-0.92) and 0.93 (95 % CI: 0.90-0.97). There was an association of elevated WHtR with higher levels of IL-6 and CRP (p < 0.05). Conclusion: the predictive capacity of WHtR for obesity was excellent. Elevated values of the WHtR were associated with early inflammatory markers. This study contributed to the identification of cut-off points for simple and low-cost anthropometric indicators.

Introducción: Introducción: la obesidad aumenta las moléculas inflamatorias y el riesgo cardiovascular incluso en poblaciones jóvenes. Se están investigando nuevos indicadores, incluida la relación cintura-altura (RCE) para predecir la obesidad y la relación con los marcadores inflamatorios en la infancia y la adolescencia. Objetivo: identificar los puntos de corte de la RCE para determinar la obesidad y su asociación con marcadores inflamatorios en adolescentes de São Luís, estado de Maranhão, Brasil. Métodos: se trata de un estudio transversal con 2.209 adolescentes de 18 y 19 años pertenecientes a la tercera etapa de la cohorte de nacimiento denominada "RPS", realizado en 2016. Se identificó el área total bajo la curva ROC (AUC) para evaluar la capacidad predictiva del RCE en relación al porcentaje de grasa corporal (%GC), obtenido a través del pletismografía por desplazamiento de aire (PDA). Se evaluó la asociación de la RCE con los marcadores inflamatorios interleucina-6 (IL-6), factor de necrosis tumoral (TNF-α) y proteína C reactiva (PCR). Resultados: se halló una prevalencia de obesidad por %GC del 10,3 % en hombres y 40,4 % en mujeres. Los puntos de corte para la RCE fueron 0,50 para mujeres y 0,51 para hombres, con un AUC de 0,90 (IC 95 %: 0,88-0,92) y 0,93 (IC 95 %: 0,90-0,97). Hubo una asociación de RCE de nivel superior con niveles más altos de IL-6 y PCR (p < 0,05). Conclusión: la capacidad de predicción de la RCE para la obesidad fue excelente y los valores elevados de RCE se asociaron con marcadores inflamatorios tempranos. Este estudio contribuyó a la identificación de puntos de corte para indicadores antropométricos simples y de bajo coste.

Decreased level of soluble receptor activator of nuclear factor-κß ligand (sRANKL) in overweight and obese children.

Introduction: Childhood obesity contributes to the development of cardiovascular diseases. The molecular pathway - receptor activator of nuclear factor-κß ligand (RANKL), its receptor RANK and osteoprotegerin (OPG) - takes part not only in bone metabolism but is also involved in the atherosclerosis process. RANKL stimulates osteogenic differentiation and calcification of vascular smooth cells. The associations between the OPG-sRANKL system and various cardiovascular risk factors were displayed. We aimed to evaluate the relationships between serum sRANKL (soluble RANKL) levels and the OPG/sRANKL ratio with cardiometabolic risk factors in overweight and obese children. Material and methods: The study included 70 children with overweight and obesity (mean age 13.0 ± 2.8) and 35 age-matched normal weight, healthy peers as a control group. In all patients, anthropometric measurements and laboratory tests were performed. Additionally, an oral glucose tolerance test (OGTT) was made only in overweight and obese children. Atherogenic and insulin resistance indices were calculated. Results: Overweight and obese children had lower sRANKL levels compared to the control group (median 276.95 vs 325.90, p=0.011), and consequently a higher OPG/sRANKL ratio (0.02 vs 0.01, p = 0.013). The studied children in the lowest quartile of sRANKL levels had higher body weight, Body Mass Index, waist circumference and increased glucose and insulin levels 60 minutes after OGTT and higher uric acid values compared to children in the highest quartile. In multivariable linear regression analysis sRANKL negatively correlated only with uric acid (ß = - 0.508, p = 0.041). No association was found for the OPG/sRANKL ratio. Conclusion: Excess fat mass seems to alter the OPG/RANKL ratio mainly by reducing serum sRANKL levels. The correlation between sRANKL and uric acid may suggest a contribution of the OPG-sRANKL system in the cardiometabolic process, but that observation should be confirmed in future studies.

Association between alanine aminotransferase as surrogate of fatty liver disease and physical activity and sedentary time in adolescents with obesity.

To compare patterns of sedentary (SED) time (more sedentary, SED + vs less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA + vs less active, MVPA-), and combinations of behaviors (SED-/MVPA + , SED-/MVPA-, SED + /MVPA + , SED + /MVPA-) regarding nonalcoholic fatty liver diseases (NAFLD) markers. This cross-sectional study included 134 subjects (13.4 ± 2.2 years, body mass index (BMI) 98.9 ± 0.7 percentile, 48.5% females) who underwent 24-h/7-day accelerometry, anthropometric, and biochemical markers (alanine aminotransferase (ALT) as first criterion, and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), AST/ALT ratio as secondary criteria). A subgroup of 39 patients underwent magnetic resonance imaging-liver fat content (MRI-LFC). Hepatic health was better in SED- (lower ALT, GGT, and MRI-LFC (p < 0.05), higher AST/ALT (p < 0.01)) vs SED + and in MVPA + (lower ALT (p < 0.05), higher AST/ALT (p < 0.01)) vs MVPA- groups after adjustment for age, gender, and Tanner stages. SED-/MVPA + group had the best hepatic health. SED-/MVPA- group had lower ALT and GGT and higher AST/ALT (p < 0.05) in comparison with SED + /MVPA + group independently of BMI. SED time was positively associated with biochemical (high ALT, low AST/ALT ratio) and imaging (high MRI-LFC) markers independently of MVPA. MVPA time was associated with biochemical markers (low ALT, high AST/ALT) but these associations were no longer significant after adjustment for SED time. CONCLUSION: Lower SED time is associated with better hepatic health independently of MVPA. Reducing SED time might be a first step in the management of pediatric obesity NAFLD when increasing MVPA is not possible. WHAT IS KNOWN: • MVPA and SED times are associated with cardiometabolic risks in youths with obesity. • The relationships between NAFLD markers and concomitant MVPA and SED times have not been studied in this population. WHAT IS NEW: • Low SED time is associated with healthier liver enzyme profiles and LFC independent of MVPA. • While low SED/high MVPA is the more desirable pattern, low SED/low MVPA pattern would have healthier liver enzyme profile compared with high MVPA/high SED, independent of BMI, suggesting that reducing SED time irrespective of MVPA is needed to optimize liver health.

Relation of serum irisin levels to obesity and non-alcoholic fatty liver disease.

BACKGROUND: Irisin is a newly defined myokine which is induced by exercise, which stimulates white fat cells to have the characteristics of brown adipose tissue cell. It thereby causes thermogenesis, energy and weight loss and improvement in insulin sensitivity. These effects of irisin suggest that it may be associated with obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD). METHODS: The aim of the present study was to determine the relationship of serum irisin levels in obese children with NAFLD. A total of 60 pubertal obese adolescents (age range: 11-18 yrs) as well as age and sex matched 28 healthy children were included in the study. Thirty of obese patients had NAFLD. RESULTS: The median irisin levels were lower in the obese patients both with and without NAFLD when compared with the control group. NAFLD group had a higher BMI than obese controls, however, the irisin levels were not different between these groups. The irisin levels were negatively correlated with BMI, BMI SDS, waist, hip and arm circumferences, waist/hip ratio, triceps-biceps skinfold thickness and AST, ALT levels in the all study groups. However, it was positively correlated with BMI, BMI SDS and waist and hip circumference in the entire obese group and positively with BMI SDS in the NAFLD subgroup. CONCLUSIONS: Consequently, circulating irisin levels are lower in obese adolescents and negatively correlated with body adiposity. In NAFLD patients, it may be related to steatosis and may decrease with liver damage.

Elevated neurotensin levels among obese adolescents may be related to emotion dysregulation and impulsivity: a cross-sectional, case-control study.

BACKGROUND: In this study, we aimed to evaluate the serum neurotensin (NT) levels and their relationships with self-reported anxiety, emotion regulation skills and impulsivity in healthy and obese adolescents. METHODS: Adolescents who gained weight between 12- 17 years of age and who were above the 95th percentile (p) for body mass index (BMI) > 95p were compared with age- and gender-matched healthy adolescents with a BMI of 3-85 p. Anthropometric measurements were performed, and serum NT levels were analyzed with ELISA method in all participants. Barrat Impulsivity Scale-11 (BIS-11), Screen for Child Anxiety Related Disorders (SCARED) and Difficulties in Emotion Regulation Scale (DERS) were used for evaluating self-reported impulsivity, anxiety and emotion regulation. MANOVA with follow-up univariate ANOVAs (Bonferroni corrected) were used for group comparisons. P was set at 0.05 (two-tailed). RESULTS: Sixty-five obese and 65 healthy adolescents were included in the study. In the obese group, NT levels were significantly elevated compared to the control group. Self-reported emotion-regulation difficulties, anxiety and impulsivity were significantly elevated among obese adolescents. Serum NT levels among the obese group were positively correlated with emotion dysregulation and impulsivity scores. CONCLUSIONS: In this study, we found emotional dysregulation, anxiety, impulsivity, and serum NT levels were significantly elevated among obese adolescents compared to controls. NT levels in the obese group correlated with impulsivity and emotion dysregulation. Further studies should evaluate the potential role of NT in the etiology of psychopathology among adolescents who are obese.

Fasting Serum IGFBP-1 as a Marker of Insulin Resistance in Diverse School Age Groups.

Introduction: The known markers of insulin resistance in obese children are well studied. However, they require serial measurements and complicated calculations. The objective is to study IGFBP-1 and its relation with other known risk measures. Materials and Methods: The study included 98 New York City school students of diverse ethnic/racial backgrounds (57 males and 41 females), 11-15 years of age. Subjects were enrolled in a cross-sectional study, and anthropometric measures were collected. They underwent fasting intravenous glucose tolerance tests (IVGTT), and glucose, insulin, lipids, IGFBP-1, adiponectin and inflammatory markers were collected. Results: The subjects were stratified into 3 groups based upon the BMI Z-score. Out of all the subjects, 65.3% were in the group with a BMI Z-score <1 SDS, 16.3% subjects were in the group with a BMI Z-score of 1 to 2 SDS, and 18.4% of the subjects were in the group with a BMI Z-score of more than 2 SDS. The group with a BMI Z-score of more than 2 SDS had increased waist circumference (WC), body fat, increased fasting insulin, and triglycerides (TG). This group had decreased levels of adiponectin and HDL and low IGFBP-1 as compared to the group with BMI <1 SDS. The group with a BMI Z-score of 1 to 2 SDS had a decreased level of IGFBP-1 as compared to the group with a BMI Z-score less than 1 SDS. IGFBP-1 inversely correlated with age, WC, BMI, body fat, TG, and insulin levels. IGFBP-1 positively correlated with adiponectin and HDL levels. Conclusion: IGFBP-1 in children can identify the presence of insulin resistance in the group with BMI 1 to 2 SDS, even before the known markers of insulin resistance such as elevated triglycerides and even before decreased HDL and adiponectin levels are identified.

Urocortin Neuropeptide Levels Are Impaired in the PBMCs of Overweight Children.

The corticotropin-releasing hormone (CRH) and urocortins (UCNs) have been implicated in energy homeostasis and the cellular stress response. However, the expression of these neuropeptides in children remains unclear. Therefore, we determined the impact of obesity on their expression in 40 children who were normal weight, overweight, and had obesity. Peripheral blood mononuclear cells (PBMCs) and plasma were used to assess the expression of neuropeptides. THP1 cells were treated with 25 mM glucose and 200 µM palmitate, and gene expression was measured by real-time polymerase chain reaction (RT-PCR). Transcript levels of neuropeptides were decreased in PBMCs from children with increased body mass index as indicated by a significant decrease in UCN1, UCN3, and CRH mRNA in overweight and obese children. UCN3 mRNA expression was strongly correlated with UCN1, UCN2, and CRH. Exposure of THP1 cells to palmitate or a combination of high glucose and palmitate for 24 h increased CRH, UCN2, and UCN3 mRNA expression with concomitant increased levels of inflammatory and endoplasmic reticulum stress markers, suggesting a crosstalk between these neuropeptides and the cellular stress response. The differential impairment of the transcript levels of CRH and UCNs in PBMCs from overweight and obese children highlights their involvement in obesity-related metabolic and cellular stress.

Effect of growth hormone therapy on liver enzyme and other cardiometabolic risk factors in boys with obesity and nonalcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common causes of liver disease in children and adolescents. Although several reports have confirmed the significant correlation between NAFLD and growth hormone (GH)-insulin-like growth factor 1(IGF-1) axis, no study further investigates whether or not recombinant human GH (rhGH) treatment can improve NAFLD in obese children. METHODS: This study was a randomized, open-label study comprising 44 boys with obesity and NAFLD (11.76 ± 1.67 year) to evaluate the effects of 6 months of rhGH administration for boys with obesity and NAFLD. The subjects were randomized divided into treatment group (subjects with recombinant human GH (rhGH)) and control group for 6 months. RESULTS: After 6 months, IGF-1 increased significantly during rhGH treatment, in comparison with the control group (582.45 ± 133.00 vs. 359.64 ± 129.00 ng/ml; p < 0.001). A significant reduction in serum alanine aminotransferase(ALT) (15.00 vs. 28.00 U/L; p = 0.001), aspartate aminotransferase(AST) (20.00 vs. 24.50U/L; p = 0.004), gamma glutamyl transferase(GGT) (14.50 vs. 28.50 U/L; p < 0.001) was observed in the GH-treated boys. In addition, the rhGH group showed a significant decrease in C reactive protein (CRP) (1.17 ± 0.76 vs. 2.26 ± 1.43 mg/L) and body mass index standard deviation scores (BMI SDS) (2.28 ± 0.80 vs. 2.71 ± 0.61) than the control group (p = 0.003, p = 0.049 respectively). GH treatment also reduced low density lipoprotein cholesterol (LDL-C) (2.19 ± 0.42 vs. 2.61 ± 0.66 mmol/L; p = 0.016) and increased high density lipoprotein cholesterol (HDL-C) (1.30 vs. 1.15 mmol/L; p = 0.005), and there were no changes in total cholesterol (TC), triglycerides (TG) and uric acid(UA) between the treatment group and the control group. CONCLUSION: Our findings suggest that 6 months treatment with rhGH may be beneficial for liver enzyme and can improve obesity-related other cardiovascular and metabolic complications in boys with obesity and NAFLD.

Untargeted Metabolomics Analysis of the Serum Metabolic Signature of Childhood Obesity.

Obesity rates among children are growing rapidly worldwide, placing massive pressure on healthcare systems. Untargeted metabolomics can expand our understanding of the pathogenesis of obesity and elucidate mechanisms related to its symptoms. However, the metabolic signatures of obesity in children have not been thoroughly investigated. Herein, we explored metabolites associated with obesity development in childhood. Untargeted metabolomic profiling was performed on fasting serum samples from 27 obese Caucasian children and adolescents and 15 sex- and age-matched normal-weight children. Three metabolomic assays were combined and yielded 726 unique identified metabolites: gas chromatography-mass spectrometry (GC-MS), hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC-MS/MS), and lipidomics. Univariate and multivariate analyses showed clear discrimination between the untargeted metabolomes of obese and normal-weight children, with 162 significantly differentially expressed metabolites between groups. Children with obesity had higher concentrations of branch-chained amino acids and various lipid metabolites, including phosphatidylcholines, cholesteryl esters, triglycerides. Thus, an early manifestation of obesity pathogenesis and its metabolic consequences in the serum metabolome are correlated with altered lipid metabolism. Obesity metabolite patterns in the adult population were very similar to the metabolic signature of childhood obesity. Identified metabolites could be potential biomarkers and used to study obesity pathomechanisms.

Tryptophan Metabolism Is Associated with BMI and Adipose Tissue Mass and Linked to Metabolic Disease in Pediatric Obesity.

The obesity epidemic has contributed to an escalating prevalence of metabolic diseases in children. Overnutrition leads to increased tryptophan uptake and availability. An association between the induction of the tryptophan catabolic pathway via indoleamine 2,3-dioxygenase (IDO) activity and obesity-related inflammation has been observed. This study aimed to investigate the impact of pediatric obesity on tryptophan metabolism and the potential relationship with metabolic disease. In this prospective cohort study, plasma kynurenine, tryptophan, and serotonin levels were measured by ELISA, and IDO activity was estimated by calculating the kynurenine/tryptophan ratio in a clinically characterized population with severe obesity (BMI ≥ 97th percentile) aged 9 to 19 (n = 125). IDO activity and its product kynurenine correlated with BMI z-score and body fat mass, whereas concentrations of serotonin, the alternative tryptophan metabolite, negatively correlated with these measures of adiposity. Kynurenine and tryptophan, but not serotonin levels, were associated with disturbed glucose metabolism. Tryptophan concentrations negatively correlated with adiponectin and were significantly higher in prediabetes and metabolically unhealthy obesity. In conclusion, BMI and body fat mass were associated with increased tryptophan catabolism via the kynurenine pathway and decreased serotonin production in children and adolescents with severe obesity. The resulting elevated kynurenine levels may contribute to metabolic disease in obesity.

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.

Responsiveness on metabolic syndrome criteria and hepatic parameters after 12 weeks and 24 weeks of multidisciplinary intervention in overweight adolescents.

PURPOSE: This study aimed to evaluate the effect and individual responsiveness after 12 (12wk) and 24 weeks (24wk) of physical exercise (PE) and nutritional guidance (NG) on metabolic syndrome (MetS) criteria and hepatic parameters in overweight adolescents. METHODS: The study comprised 94 overweight adolescents, aged between 10 and 16 years old, from both sexes, allocated into groups: PE and NG (PENGG, n = 64) and control with NG (NGCG, n = 30). Variables were collected at baseline, 12wk, and 24wk. Weight, height, abdominal circumference (AC), blood pressure, and peak oxygen consumption (VO2peak), as well as insulin, triglycerides (TAG), high-density lipoprotein (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. HOMA-IR and QUICKI were calculated. PE session consisted of 45 min of indoor cycling, 45 min of walking, and 20 min of stretching, three times a week. The NG consisted of three collective sessions in the first 12wk. Anova, effect size, and prevalence of responders were used for statistical analysis. RESULTS: The PENGG12wk reduced anthropometric and metabolic measurements, while increased VO2peak and HDL-c. The PEG24wk promoted anthropometric, blood pressure, metabolic, and VO2peak improvements, but participants without PE returned to pre-exercise status and presented worsening AST and ALT concentrations. Frequencies of respondents in PENGG12wk versus (vs) NGCG12wk were, respectively, AC (69.1% vs 17.6%, p < 0.01), HDL-c (87.2% vs 23.5%, p < 0.01), TAG (67.3% vs 41.7%, p = 0.05) and ALT (45.5% vs 5,9%; p = 0.003). CONCLUSION: Interventions with PE were effective to reduce MetS components in 12wk and maintenance in 24wk, showing anthropometric, metabolic, and VO2peak improvements. Higher individual responses were observed in 12wk and in 24wk, important changes in overweight adolescent's therapy. LEVEL OF EVIDENCE: Level I, evidence obtained from well-designed controlled trials randomization. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Brazilian Registry of Clinical Trials (RBR-4v6h7b) and date of registration April 4th, 2020.

BMI metrics and their association with adiposity, cardiometabolic risk factors, and biomarkers in children and adolescents.

BACKGROUND: There are limited data comparing the relative associations of various BMI metrics with adiposity and cardiometabolic risk factors in youth. OBJECTIVE: Examine correlations of 7 different BMI metrics with adiposity, cardiometabolic risk factors, and biomarkers (i.e. blood pressure, waist circumference, cholesterol, leptin, insulin, high molecular weight adiponectin, high-sensitivity c-reactive protein (hsCRP)). METHODS: This was a cross-sectional analysis of youth in all BMI categories. BMI metrics: BMI z-score (BMIz), extended BMIz (ext.BMIz), BMI percentile (BMIp), percent of the BMI 95th percentile (%BMIp95), percent of the BMI median (%BMIp50), triponderal mass index (TMI), and BMI (BMI). Correlations between these BMI metrics and adiposity, visceral adiposity, cardiometabolic risk factors and biomarkers were summarized using Pearson's correlations. RESULTS: Data from 371 children and adolescents ages 8-21 years old were included in our analysis: 52% were female; 20.2% with Class I obesity, 20.5% with Class II, and 14.3% with Class III obesity. BMIp consistently demonstrated lower correlations with adiposity, risk factors, and biomarkers (r = 0.190-0.768) than other BMI metrics. The %BMIp95 and %BMIp50 were marginally more strongly correlated with measures of adiposity as compared to other BMI metrics. The ext.BMIz did not meaningfully outperform BMIz. CONCLUSION: Out of all the BMI metrics evaluated, %BMIp95 and %BMIp50 were the most strongly correlated with measures of adiposity. %BMIp95 has the benefit of being used currently to define obesity and severe obesity in both clinical and research settings. BMIp consistently had the lowest correlations. Future research should evaluate the longitudinal stability of various BMI metrics and their relative associations with medium to long-term changes in adiposity and cardiometabolic outcomes in the context of intervention trials.

How Reliable are Commercially Available Glypican4 ELISA Kits?

OBJECTIVE: Glypican4 is an interesting new adipokine, which seems to play an important role in developmental processes and is potentially associated with metabolic changes in obesity and type 2 diabetes mellitus. Currently, only a few studies examined glypican4 in human blood, mainly in adults. DESIGN, PATIENTS AND MEASUREMENTS: The aim of our study was to investigate glypican4 serum levels in lean, overweight, and obese children and adolescents, to unravel a possible association between glypican4 serum levels and parameters of obesity and insulin resistance. In order to determine a suitable method for investigating glypican4 serum levels, we validated two commercially available human glypican4 ELISA kits, using serum and plasma samples of an obese, insulin-resistant patient, and a healthy control subject, a human recombinant glypican4 protein fragment and glypican4-overexpressing cell lysate. RESULTS: Using ELISA kit #1 we were not able to detect values above background level, apart from standard curve values. ELISA kit #2 initially seemed suitable to measure glypican4, but further validation experiments showed non-linearity of serial dilutions, no recognition of a human recombinant glypican4 protein fragment and non-linearity in the recovery of glypican4-overexpressing cell lysate. In addition, there was a considerable decrease (approx. 68%) of measured values between two experiments, performed at different time points with aliquots of the same serum sample. Contrary to that, further experiments found sample stability not to be compromised. CONCLUSIONS: Extensive evaluation of the performance of two commercially available ELISA kits led to the conclusion that none of them is applicable for the measurement of glypican4 in human blood samples.

Vitamin D supplementation and cardiometabolic risk factors among diverse schoolchildren: a randomized clinical trial.

BACKGROUND: There remains a lack of evidence demonstrating a potential relationship between vitamin D and cardiometabolic risk among children. OBJECTIVES: We examined the effect of 3 different dosages of vitamin D on cardiometabolic risk factors among children at risk of deficiency. METHODS: Racially diverse schoolchildren aged 8-15 y were randomly assigned in a double-blind fashion to supplementation with 600, 1000, or 2000 IU vitamin D3/d for 6 mo. Changes in HDL cholesterol, triglycerides, LDL cholesterol, total cholesterol, and blood glucose over 6 mo and at 12 mo (6 mo post-supplementation) were assessed. Subgroup analyses were also performed by weight status and race. RESULTS: Among 604 children, 40.9% were vitamin D-inadequate at baseline (<20 ng/mL; mean ± SD: 22.0 ± 6.8 ng/mL), 46.4% were overweight/obese, and 60.9% had ≥1 suboptimal blood lipids or glucose. Over 6 mo, serum 25-hydroxyvitamin D increased in all 3 dosage groups from baseline (mean ± SE change: 4.4 ± 0.6 ng/mL, 5.7 ± 0.7 ng/mL, and 10.7 ± 0.6 ng/mL for 600, 1000, and 2000 IU/d, respectively; P < 0.001). Whereas HDL cholesterol and triglycerides increased in the 600 IU group (P = 0.002 and P = 0.02, respectively), LDL cholesterol and total cholesterol decreased across dosage groups. At 6 mo post-supplementation, HDL cholesterol remained elevated in the 600 and 1000 IU groups ( P < 0.001 and P = 0.02, respectively) whereas triglycerides remained elevated in the 1000 and 2000 IU groups (P = 0.04 and P = 0.006, respectively). The suppression of LDL cholesterol and total cholesterol persisted in the 2000 IU group only (P = 0.04 and P < 0.001, respectively). There were no significant changes in blood glucose and similar responses were observed overall by weight status and racial groups across dosages. CONCLUSIONS: Vitamin D supplementation demonstrated generally positive effects on HDL cholesterol, LDL cholesterol, and total cholesterol, especially at the lower dosage of 600 IU/d, with several significant changes persisting during the post-supplementation period. Increases in triglycerides across dosage groups may be due to natural changes during adolescence warranting further study.This trial was registered at clinicaltrials.gov as NCT01537809.

Obesity-Induced Insulin Resistance Is Mediated by High Uric Acid in Obese Children and Adolescents.

Objective: This study aimed to evaluate whether serum uric acid (SUA) plays a mediating role in the development of insulin resistance (IR) in obese children and adolescents. Methods: A total of 369 participants aged 4-17 years with obesity who attended the Nutrition Outpatient Clinic for Obesity at Xinhua Hospital from January 2012 to January 2019 were recruited for this retrospective study. We classified participants into two groups on the basis of HOMA-IR values: the low HOMA-IR group (< 3.16) (n = 222) and the high HOMA-IR group (≥ 3.16) (n = 147). Results: The univariate analysis found that the high HOMA-IR group had higher BMI, SUA, and fasting insulin (FINS) (P < 0.05). Multiple linear regression analysis and mediating effect analysis indicated that body mass index (BMI) could directly regulate FINS and HOMA-IR (both P < 0.05). The results from the mediating effect analysis found that UA partially played an indirect role in the link between BMI, FINS and HOMA-IR (both P < 0.05) but had no effect on fasting blood glucose (P > 0.05). Conclusions: SUA should be investigated in obesity and plays a partial mediating role in insulin resistance induced by obesity in obese children and adolescents.

Time-Limited Eating and Continuous Glucose Monitoring in Adolescents with Obesity: A Pilot Study.

Due to its simplicity, time-limited eating (TLE) may represent a more feasible approach for treating adolescents with obesity compared to other caloric restriction regimens. This pilot study examines the feasibility and safety of TLE combined with continuous glucose monitoring (CGM) in adolescents. Fifty adolescents with BMI ≥95th percentile were recruited to complete a 12-week study. All received standard nutritional counseling, wore a CGM daily, and were randomized to: (1) Prolonged eating window: 12 h eating/12 h fasting + blinded CGM; (2) TLE (8 h eating/16 h fasting, 5 days per week) + blinded CGM; (3) TLE + real-time CGM feedback. Recruitment, retention, and adherence were recorded as indicators of feasibility. Weight loss, dietary intake, physical activity, eating behaviors, and quality of life over the course of the intervention were explored as secondary outcomes. Forty-five participants completed the study (16.4 ± 1.3 years, 64% female, 49% Hispanic, 75% public insurance). There was high adherence to prescribed eating windows (TLE 5.2 d/wk [SD 1.1]; control 6.1 d/wk [SD 1.4]) and daily CGM wear (5.85 d/wk [SD 4.8]). Most of the adolescents (90%) assigned to TLE reported that limiting their eating window and wearing a CGM was feasible without negative impact on daily functioning or adverse events. There were no between-group difference in terms of weight loss, energy intake, quality of life, physical activity, or eating behaviors. TLE combined with CGM appears feasible and safe among adolescents with obesity. Further investigation in larger samples, with a longer intervention duration and follow-up assessments are needed.

Lipidomic profiling reveals distinct differences in plasma lipid composition in overweight or obese adolescent students.

INTRODUCTION: The relationship between dyslipidemia and obesity has been widely reported, but the global lipid profiles associated with the development of obesity still need to be clarified. An investigation into the association between the lipidomic plasma profile and adolescent obesity may provide new insights into the development of obesity. METHODS: Mass spectrometry coupled with liquid chromatography was applied to detect the global lipidome in the fasting plasma from 90 Chinese adolescents, including 34 obese adolescents, 26 overweight adolescents, and 30 adolescents with a normal body mass index (BMI). All participants underwent anthropometric measurements by using InBody. Clinical biochemical indicators were measured by Cobas Elecsys. RESULTS: Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features among obese students, exhibiting characteristics close to overweight students, but differing significantly from normal students. Compared with normal and overweight students, levels of triglyceride (TG), 18-hydroxycortisol, isohumulinone A, and 11-dihydro-12-norneoquassin were up-regulated in the obese group, while phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC (LPC), lysoPE (LPE), and phosphatidylinositol (PI) were significantly down-regulated in the obese group. Then, we conducted Venn diagrams and selected 8 significant metabolites from the 3 paired comparisons. Most of the selected features were significantly correlated with the anthropometric measurements. CONCLUSIONS: This study demonstrated evidence for a relationship between the eight significant metabolites with obese adolescents. These lipid features may provide a basis for evaluating risk and monitoring the development of obesity.