Lean Children Research Articles

Longitudinal analysis of vitamin D levels considering sunshine duration and suggestion for a standardised approach for vitamin D supplementation in children and adolescents with obesity

BackgroundChildren with obesity have low 25 hydroxy-vitamin D (25-OH-D3) levels compared to lean children. Recommendations on when to start vitamin D supplementation differ largely between countries. Longitudinal data on 25-OH-D3 levels to guide treatment decisions are scarce since they are largely influenced by solar radiation and are difficult to compare.MethodsWe carried out a retrospective analysis of multiple 25-OH-D3 and parathyroid hormone (PTH) measurements in a cohort of 543 patients without vitamin D supplementation. All measurements were taken at the local paediatric obesity clinic as documented in the German-Austrian-Swiss APV (Prospective Documentation of Overweight Children and Adolescents) registry from 2009 to 2019. Serial 25-OH-D3 and PTH levels were adjusted for sunshine duration over the last 30 days to account for seasonal variation, as well as for sex and body mass index (BMI). We further performed an exploratory analysis of the association of sunshine duration, sex, BMI SDS (standard deviation score), abnormal lipid levels or dysglycemia with the 25-OH-D3 trend.Results229 obese patients (mean BMI SDS: 2,58 (± 0,56), 53% females, mean age: 12 (± 3) years, range: 2–21 years) with two, 115 with three and 96 with four repeated 25-OH-D3 measurements were identified. Mean adjusted 25-OH-D3 (48.2 nmol/l) and PTH (34.9 ng/l) levels remained stable over 120 weeks. 5% of the patients had an elevated PTH > 65 ng/l. High total cholesterol ≥ 200 mg/dl and high triglycerides ≥ 130 mg/dl were associated with higher 25-OH-D3 levels.ConclusionWe propose a simple method to include sunshine duration in the analysis of 25-OH-D3 levels to minimise the bias of seasonal variation. Based on our data we established the pragmatic strategy of limiting vitamin D supplementation to patients with biochemical signs of mineralisation disorders such as elevated PTH and alkaline phosphatase (AP). In children with normal PTH and AP we recommend adjustment of calcium intake and increase of outdoor activity instead.

Childhood obesity accelerates biological ageing: is oxidative stress a link?

Obesity is a multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed to estimate the connection between relative leucocyte telomere lengths (rLTL) - biomarker of cellular ageing with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both sexes. The results suggested that rLTL are significantly shorter in obese, compared with lean group (P < 0·01). Negative correlation of rLTL with total oxidant status (TOS) (Spearman's ρ = -0·365, P < 0·001) as well as with C-reactive protein (Spearman's ρ = -0·363, P < 0·001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35 % of total variability; antioxidant factor with 30 % of total variability and lipid antioxidant - biological ageing factor with 12 % of the total variability. The most important predictor of BMI > 30 kg/m2 according to logistic regression analysis was PCA-derived antioxidant factor's score (OR: 1·66, 95th Cl 1·05-2·6, P = 0·029). PCA analysis confirmed that oxidative stress importance in biological ageing is caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homoeostasis deepness, even before any overt disease occurrence.

Cytokine Response to Resistance Exercise in Children with Excess Fat and Prader-Willi Syndrome

Background: Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine that is secreted from adipose tissue and macrophages; interleukin-6 (IL-6), secreted from adipose tissue, macrophages and skeletal muscle, has both proinflammatory and anti-inflammatory properties. Previous research showed excess adiposity leads to an increased concentration of both cytokines at rest while there is limited research on resistance exercise. Purpose: To compare IL-6 and TNF-α responses to resistance exercise in children with Prader-Willi Syndrome (PWS), a genetic cause for obesity, vs. children with normal fat mass (lean), or excess body fat (obesity) Methods: Nine children with PWS (11.4 ± 3.3 years, 45.6 ± 5.2% body fat), 11 lean children (9.2 ± 1.4 years, 18.6 ± 5.0% bodyfat), and 12 children with obesity (9.6 ± 1.3 years, 40.4 ± 5.4% body fat) participated. Children stepped onto an elevated platform wearing a weighted vest for 6 sets of 10 repetitions per leg (sets separated by 1 min of rest). Children with PWS, stepped to a platform height of 23.0 cm and wore a vest load that was computed as (20% of stature* 50% of lean body mass)/23.0 cm. For the controls, the platform height was 20% of the stature and the vest load was 50% of the lean body mass. Blood samples were obtained before (pre), immediately after (post), and during recovery from exercise (+15 and +60 min). Areas under the curve (AUC) were computed for IL-6 and TNF-α. Results: There was no group by time interaction for IL-6 ( p=0.378) but a group effect ( p=0.011) and a time effect ( p&lt;0.001). Pairwise comparisons showed 60+ (1.065 ± 0.10 pg/mL) was higher than pre (0.660 ± 0.05 pg/mL), post (0.728 ± 0.06 pg/mL), and +15 (0.764 ± 0.066 pg/mL), p&lt;0.001 for all. Children with PWS and children with obesity had higher IL-6 concentrations than lean children (0.943 ± 0.12 pg/mL and 0.951 ± 0.10 pg/mL vs. 0.519 ± 0.11 pg/mL, p≤0.038 for both). For TNF-α, there were no group by time interaction, time or group effects ( p≥0.420 for all). IL-6 AUC ( p=0.013) but not TNF-α AUC ( p=0.404) were different between groups. Children with PWS and children with obesity showed a higher IL-6 AUC than lean children (85.106 ± 41.81 pg/mL, 86.796 ± 33.60 pg/mL vs. 47.611 ± 21.00 pg/mL, p≤ 0.041 for both). Conclusion: There were no differences in IL-6 or TNF-α responses to exercise based on having PWS or having excess body fat in children. However, excess body fat was associated with higher IL-6 concentration and AUC. Peak concentrations for IL-6 were observed at 60 minutes after exercise similar to other studies. Potentially, IL-6 concentrations immediately post-exercise were not elevated because the exercise protocol was not of high intensity or long enough. Study funded by the US Army Medical Research and Material Command Contract W81XWH-08-1-0025 (DAR). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Parental obesity predisposes to exacerbated metabolic and inflammatory disturbances in childhood obesity within the framework of an altered profile of trace elements

BackgroundFamily history of obesity is known to increase the odds of developing childhood obesity in the offspring, but its influence in underlying molecular complications remains unexplored.Subjects/MethodsHere, we investigated a population-based cohort comprising children with obesity, with and without parental obesity (PO+, N = 20; PO−, N = 29), and lean healthy children as controls (N = 30), from whom plasma and erythrocyte samples were collected to characterize their multi-elemental profile, inflammatory status, as well as carbohydrate and lipid metabolisms.ResultsWe found parental obesity to be associated with unhealthier outcomes in children, as reflected in increased blood insulin levels and reduced insulin sensitivity, unfavorable lipid profile, and pro-inflammatory milieu. This was accompanied by moderate alterations in the content of trace elements, including increased copper-to-zinc ratios and iron deficiency in circulation, as well as metal accumulation within erythrocytes.ConclusionsTherefore, we hypothesize that family history of obesity could be an important risk factor in modulating the characteristic multi-elemental alterations behind childhood obesity, which in turn could predispose to boost related comorbidities and metabolic complications.

Child-to-adult body size change and risk of type 2 diabetes and cardiovascular disease.

Childhood overweight increases the risk of type 2 diabetes and cardiovascular disease in adulthood. However, the impact of childhood leanness on adult obesity and disease risk has been overlooked. We examined the independent and combined influences of child and adult body size on the risk of type 2 diabetes and cardiovascular disease. Data from the UK Biobank on 364,695 individuals of European ancestry and free of type 2 diabetes and cardiovascular disease were divided into nine categories based on their self-reported body size at age 10 and measured BMI in adulthood. After a median follow-up of 12.8 years, 33,460 individuals had developed type 2 diabetes and/or cardiovascular disease. We used Cox regression models to assess the associations of body size categories with disease incidence. Individuals with low body size in childhood and high body size in adulthood had the highest risk of type 2 diabetes (HR 4.73; 95% CI 4.50, 4.99), compared to those with average body size in both childhood and adulthood. This was significantly higher than the risk in those with high body size in both childhood and adulthood (HR 4.05; 95% CI 3.84, 4.26). By contrast, cardiovascular disease risk was determined by adult body size, irrespective of childhood body size. Low body size in childhood exacerbates the risk of type 2 diabetes associated with adult obesity but not the risk of cardiovascular disease. Thus, promoting healthy weight management from childhood to adulthood, among lean children, is crucial.

Identification of novel circulating miRNAs biomarkers for healthy obese and lean children

BackgroundThe prevalence of childhood obesity and overweight has risen globally, leading to increased rates of metabolic disorders. Various factors, including genetic, epigenetic, and environmental influences such as diet and physical activity, contribute to pediatric obesity. This study aimed to identify specific circulating miRNAs as potential biomarkers for assessing obesity in children.MethodsThirty children, including 15 obese and 15 extremely thin individuals, were selected for this study. MiRNA expression in circulating plasma was assessed using miRNA microarrays. The reliability of differential miRNA expression was confirmed using TaqMan qPCR. The correlation between miRNAs and obesity was analyzed through multiple linear regression, receiver operator characteristic (ROC) curve analysis, and odds ratio (OR) calculations. Bioinformatics tools were utilized to identify target genes for the selected miRNAs, and a functional network map was constructed.ResultsA total of 36 differentially expressed miRNAs were identified through gene chip analysis, and TaqMan qPCR validation confirmed the upregulation of seven miRNAs: hsa-miR-126-3p, hsa-miR-15b-5p, hsa-miR-199a-3p, hsa-miR-20a-5p, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-24-3p. Among these, hsa-miR-15b-5p and hsa-miR-223-3p exhibited a statistically significant difference except for hsa-miR-23a-3p. These two miRNAs showed more predicted target genes related to obesity than others. Multiple linear regression analysis revealed an association between obesity and hsa-miR-15b-5p and hsa-miR-223-3p [10.529 (4.974–16.084), -10.225 (-17.852~ -2.657)]. Even after adjusting for age and sex, these two miRNAs remained associated with obesity [8.936 (3.572–14.301), -8.449(-15.634~ -1.303)]. The area under the ROC curve (AUC) reached values of 0.816, 0.711, and 0.929, respectively. Odds ratio analysis demonstrated a significant correlation between obesity and hsa-miR-15b-5p (OR = 143, 95% CI 5.80 to 56,313, p = 0.024) and between obesity and hsa-miR-223-3p (OR = 0.01, 95% CI 0.00 to 0.23, p = 0.037). Importantly, hsa-miR-15b-5p was found to have numerous target genes associated with the FoxO, insulin, Ras, and AMPK signaling pathways.ConclusionsDifferential miRNA expression profiles in the circulation of obese children compared to controls suggest underlying metabolic abnormalities. Hsa-miR-15b-5p and hsa-miR-223-3p may be considered as molecular markers for the screening of obese children and populations at risk of developing metabolic syndrome.

Exploring Gut Microbiota and the Influence of Physical Activity Interventions on Overweight and Obese Children and Adolescents: A Systematic Review.

The recognition that the gut microbiota of obese children differs from lean children has grown, and some studies suggest that physical activity positively influences the gut microbiota. This systematic review explores the changes in the gut microbiota composition of obese and non-obese children and adolescents and provides an understanding of the effects of physical activity interventions in modulating their microbiota. The PRISMA protocol was used across PubMed, Scopus, and Web of Science. Overall, twenty-four research papers were included in accordance with the chosen inclusion and exclusion criteria, eighteen studies compared the gut microbiota of obese and normal-weight children and adolescents, and six studies explored the effect of physical activity interventions on the gut microbiota. The analysis indicated that obese gut microbiota is reduced in Bacteroidetes, Bifidobacterium and alpha diversity but enriched in Proteobacteria and Lactobacillus. Interventions with physical activity seem to improve the alpha diversity and beneficial bacteria linked to body weight loss in children and adolescents. The gut microbiota of obese children exhibited a remarkably individual variation. More interventions are needed to clearly and accurately explore the relationships between child obesity, gut microbiota, and physical activity and to develop approaches to decrease the incidence of paediatric obesity.

Higher energy flux may improve short-term appetite control in adolescents with obesity: the NEXT study.

Recent evidence suggests better appetite control in states of high-energy flux (HEF) in adults and lean children. Nevertheless, it is unknown whether this extends to youth with obesity. This study compares the effects of low, moderate or HEF on short-term appetitive control in adolescents with obesity. Sixteen adolescents with obesity (12-16 years, Tanner stages 3-5, 11 females) randomly completed three conditions: (i) low-energy flux (LEF); (ii) moderate energy flux (MEF; + 250 kcal) and (iii) HEF (HEF; + 500 kcal). Energy flux was achieved in MEF and HEF through elevated energy intake (EI) and concomitant increase in energy expenditure using cycling exercise (65 % VO2peak). Ad libitum EI, macronutrient intake and relative EI were assessed at dinner, subjective appetite sensations taken at regular intervals and food reward measured before dinner. Ad libitum EI at dinner was greater in LEF compared with HEF (P = 0·008), and relative EI (REI) was higher in LEF compared with MEF (P = 0·003) and HEF (P < 0·001). The absolute consumption of carbohydrates was lower in LEF compared with MEF (P = 0·047) and HEF (P < 0·001). Total AUC for hunger and desire to eat was lower in HEF compared with LEF (P < 0·001) and MEF (P = 0·038). Total AUC for prospective food consumption was lower on HEF compared with LEF (P = 0·004). Food choice sweet bias was higher in HEF (P = 0·005) compared with LEF. To conclude, increasing energy flux may improve short-term appetite control in adolescents with obesity.

Challenges in body composition assessment using air-displacement plethysmography by BOD POD in pediatric and young adult patients

Air-Displacement-Plethysmography (ADP) by BOD POD is widely used for body fat assessment in children. Although validated in healthy subjects, studies about use in pediatric patients are lacking. We evaluated user experience and usability of ADP measurements with the BOD POD system in healthy children and pediatric and young adult patients. Using the experiences of seven cohort studies, which included healthy children and patients aged 2-22 years, we retrospectively evaluated the user experience with the User Experience Questionnaire (UEQ) (n=13) and interviews (n=7). Technical performance was studied using the quality control data collected by the ADP-system. From 2016 to 2022, 1606 measurements were scheduled. BOD POD was mostly rated 'user-friendly', with a generally neutral evaluation on all scales of the UEQ. However, questionable reliability and validity of the results were frequently (86%) reported. We found a high technical failure-rate of the device, predominantly in stability (17%) and accuracy of the measurement (12%), especially in the 'pediatric option' for children aged <6 years. Measurement failure-rate was 38%, mostly due to subject's fear or device failure, especially in young and lean children, and in children with physical and/or intellectual disabilities. We conclude that ADP by BOD POD in children and young adults is non-invasive and user-friendly. However, in specific pediatric populations, BOD POD has several limitations and high (technical) failure-rates, especially in young children with aberrant body composition. We recommend caution when interpreting body composition results of pediatric patients as assessed with BOD POD using the current default settings.

Frequency and characteristics of diabetes in lipodystrophies and insulin receptoropathies compared with type 1 and type 2: results from the multicenter DPV registry.

To investigate the frequency, treatment, and outcome of patients with diabetes due to severe insulin resistance syndromes (SIRS). Based on data from the multicenter prospective Diabetes Registry DPV, we analyzed diagnosis, treatment, and outcome of 636,777 patients with diabetes from 1995 to 2022. Diabetes due to SIRS was documented in 67 cases (62.7% females), 25 (37%) had lipodystrophies (LD) and 42 (63%) had congenital defects of insulin signaling. The relative frequency compared to type 1 diabetes (T1D) was about 1:2300. Median age at diabetes diagnosis in patients with SIRS was 14.8 years (interquartile range (IQR) 12.8-33.8). A total of 38 patients with SIRS (57%) received insulin and 34 (51%) other antidiabetics, mostly metformin. As high as 16% of patients with LD were treated with fibrates. Three out of eight patients with generalized LD (37.5%) were treated with metreleptin and one patient with Rabson-Mendenhall syndrome was treated with recombinant insulin-like growth factor 1. The median glycated hemoglobin level at follow-up was 7.1% (54 mmol/mol). Patients with LD had higher triglycerides than patients with T1D and T2D (P < 0.001 and P = 0.022, respectively), and also significantly higher liver enzymes and lower high-density lipoprotein cholesterol than patients with T1D (P < 0.001). Patients with insulin receptor disorders were significantly less likely to be treated with antihypertensive medication than patients with T2D (P = 0.042), despite having similar levels of hypertension. Diabetes due to SIRS is rarely diagnosed and should be suspected in lean children or young adults without classical T1D. Awareness of cardiovascular risk factors in these patients should be raised.

The Intake of Antioxidant Capacity of Children Depends on Their Health Status.

The gastrointestinal digestion of food and further gut microbial activity render a myriad of different molecules that could be responsible for the biological activities that are classically assigned to their parent compounds. This has been previously shown for some phytochemicals whose antioxidant capacity was either increased or decreased after being metabolized by gut microbes. Whether a global antioxidant capacity that is extracted from food is determined by the gut microbial community structure is still not well described. In the present study, we in vitro digested and fermented 48 different foods that were submitted to different culinary treatments using the stools of lean children, obese children, celiac children and children with an allergy to cow’s milk proteins. Their antioxidant capacities were assessed with the DPPH and FRAP assays, and the percentage that each food contributed to their daily antioxidant intake as well as their antioxidant capacity by portion size was inferred. Overall, cereals, fruits and vegetables displayed a higher contribution to their daily antioxidant intake, while tubers, fish and meat exhibited a higher antioxidant capacity by serving size. The food that was fermented in the lean children’s and those children that were allergic to cow’s milk protein’s fecal material, showed a higher antioxidant capacity, which could imply that there is a larger role of the gut microbiota in this area.

Macronutrient and Micronutrient Intake in Adolescents With Non-alcoholic Fatty Liver Disease: The Association With Disease Severity.

While dietary changes are recommended to treat pediatric non-alcoholic fatty liver disease (NAFLD), the role of specific nutrients in disease progression is unclear. The objective of this study is to (1) assess the macronutrient and micronutrient intake in adolescents with liver biopsy proven NAFLD [with and without non-alcoholic steatohepatitis (NASH)] and lean controls; (2) determine nutritional predictors of disease severity amongst these groups. Adolescents with biopsy-proven NAFLD and lean controls completed the Harvard Food Frequency Questionnaire. Twenty-eight NAFLD and 15 lean controls were studied. NAFLD with (n = 20) and without NASH (n = 8) had similar total calorie, protein, fat, and carbohydrate intake. Subjects with NASH had higher total sugar (122.3 ± 48.3 vs 83.1 ± 38.8 g), glucose (24.3 ± 9.3 vs 15.2 ± 7.5 g), sucrose (42.3 ± 16.9 vs 28.8 ± 11.7 g), and fructose (29.4 ± 12.5 vs 18.1 ± 8.0 g) intake than those with NAFLD but without NASH ( P < 0.05). Both NAFLD groups had similar micronutrient intake. Alanine aminotransferase (ALT) correlated with total caloric intake ( ρ = 0.4; P = 0.04). Total carbohydrate calories correlated with a higher NAS summary score ( ρ = 0.38; P = 0.04) and lobular inflammation ( ρ = 0.50; P = 0.007). Percent calories from added sugar and glucose correlated with worsening NAS summary score ( ρ = 0.44, P = 0.02; ρ = 0.48, P = 0.009) and lobular inflammation ( ρ = 0.51, P = 0.006; ρ = 0.53, P = 0.004). Percent calories from fructose correlated with lobular inflammation ( ρ = 0.56; P = 0.002). Total daily calories, protein, fat, carbohydrate, and micronutrient intake were similar between NAFLD and lean controls. NASH patients consume similar total calories, protein, and fat as those without NASH, but have significantly higher sugar intake. NAFLD and lean children, however, have similar macro/micronutrient intake. Histologic disease severity correlates with total carbohydrate and added sugar intake, supporting a role for simple sugar intake in NAFLD progression.

The Gut Microbiota of Obese Children Releases Lower Antioxidant Capacity from Food than That of Lean Children.

The prevalence of obesity has been increasing in children over the last few decades, becoming a concern for health professionals and governments. Gut microbial community structure in obese people have been found to differ from that of lean subjects for some taxa which could result in different production of microbial metabolites. The aim of the present work was to study whether the gut microbiota from obese children extracts a different concentration of antioxidant capacity than the gut microbiota from lean children. For this purpose, different foods were in vitro digested and in vitro fermented using fecal material from obese and lean children. FRAP, DPPH and Folin-Ciocalteu methods were used to measure the antioxidant capacity released during digestion and fermentation. Overall, when using lean gut microbiota, antioxidant capacity released was higher when measured via DPPH and FRAP. Moreover, according to DPPH results, lean gut microbiota could potentially release more antioxidant power from vegetables than from animal products, while obese gut microbiota did the opposite. On the contrary, with the FRAP method obese gut microbiota released higher levels of antioxidant power from plant products than from animal products, but the final antioxidant capacity was still lower than that released by lean gut microbiota. Therefore, these results reflect that the total antioxidant capacity of foods is influenced by the gut microbiota, although whether that antioxidant capacity is released from plant or animal products can be slightly influenced by the method used for analysis.

Characterization of Post-Hypoglycemic Hyperglycemia in Children and Adolescents With Type 1 Diabetes: The EPHICA Study

BackgroundIn patients with diabetes, the dynamics in which hypoglycemia recovers impacts cardiovascular disease risk. Our study investigated the extents of “post-hypoglycemic hyperglycemia (PHH)” (i.e. hypoglycemia that recover to hyperglycemia in any circumstance) and factors likely to influence PHH characteristics in a pediatric cohort of patients with type 1 diabetes (T1D).MethodsWe collected retrospective continuous glucose monitoring (CGM) data from 142 pediatric patients with T1D to characterize episodes of PHH during a two-month follow-up period. Factors influencing PHH were determined using univariate and multivariate analyses.ResultsIn our EPHICA cohort, PHH rate was 0.6 ± 0.3 episode/day and correlated (r=0.33; p<0.0001) with hyperglycemia rate (2.6 ± 0.5 episodes/day). The global proportion of hyperglycemia corresponding to PHH was 0.22 ± 0.1, yet 14.8% of patients had more than 1/3 of hyperglycemia related to PHH. Episodes of PHH lasted 239.6 ± 124.8 minutes with a hyperglycemic peak of 258.8 ± 47.1 mg/dL. Only 12.2% of PHH occurred at night. While a younger age (<12 years) and lower body mass index (BMI) (SDS: -2 to 1.6) were associated with higher daily PHH rates, teenagers (≥12 years) and obese patients experienced longer PHH and higher hyperglycemic peaks. Parameters of glycemic variability (i.e. HbA1C, IDAA1C and GTAA1C) moderately correlated with PHH duration and related hyperglycemic peak. Multivariate analysis confirmed these results, as factors likely to influence PHH rate were phenotype (age and BMI) and glycemic variability parameters (time in range, mean glycemia, HbA1C and GTAA1C).ConclusionOur EPHICA study highlights the importance of PHH as a prominent component of hyperglycemia in some children and adolescents with T1D. Factors associated with PHH features are age, BMI and parameters of glycemic control. Young and lean children are more prone to experience hypoglycemia that recover with hyperglycemia, but adolescents and obese children tend to experience hyperglycemia of longer duration.

Prevalence and Risk Factors for Hepatic Steatosis in Children With Perinatal HIV on Early Antiretroviral Therapy Compared to HIV-Exposed Uninfected and HIV-Unexposed Children.

ObjectivesWe evaluated the prevalence and risk factors for hepatic steatosis in South African children with perinatally acquired HIV (PHIV) who started treatment early and remain on long-term antiretroviral therapy (ART) compared to HIV-uninfected children.DesignA cross-sectional study from April 2019 to October 2021. PHIV, HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled from an ongoing cohort study.MethodsAll children had transient elastography (TE) with controlled attenuation parameter (CAP). Liver enzymes, lipogram, insulin and glucose were sent after an overnight fast. Multivariable linear regression analyses identified predictors of CAP. Hepatic steatosis was defined as CAP>248kPa.Results215 children (111 [52%] male; median age 14.1 years; IQR 12.7–14.9) participated in the study, 110 PHIV, 105 HIV-uninfected (36 HEU, 69 HU). PHIV initiated ART at a median age of 2.7 months (IQR 1.8–8.5). Hepatic steatosis prevalence was 9% in PHIV, 3% in HEU and 1% in HU children (p = 0.08). However, 8% of lean (body mass index z-score ≤ +1) PHIV had hepatic steatosis compared to zero lean HEU or HU children (p = 0.03). In multivariable linear regression analysis of all PHIV, body mass index (BMI) z-score was positively associated with CAP (p = 0.001) while CD4 count (p = 0.02) and duration of suppression of HIV viraemia (p = 0.009) were negatively associated with CAP, adjusting for age, sex and ethnicity.ConclusionsHepatic steatosis prevalence was higher in lean PHIV than lean HIV-uninfected South African children. Longer suppression of HIV viraemia and higher CD4 count were associated with lower CAP and might be protective factors for hepatic steatosis in PHIV children.

Serum Chemerin and Apelin Levels in Obese Children: Relation to Endothelial Function and Inflammation from a Cross-sectional Case–Control Study

BACKGROUND: Childhood obesity is a global threat with subsequent health problems among which and most important is cardiovascular problems. It is now claimed that adipokines secreted by adipose tissue are responsible for such consequences. Newly discovered adipokines chemerin and apelin are under investigation for their link with obesity related co-morbidites. AIM: The aim of the present study was to assess the serum levels of chemerin and apelin in obese children and to explore the correlation between these two biomarkers and the inflammatory as well as the endothelial cell activation markers PATIENTS AND METHODS: This study was a cross-sectional case control study that comprised 45 pre-pubertal obese children aged (6– &lt; 12) years old of both sexes (22 males and 23 females), in addition to 45 matched age and sex lean children serving as controls (21 males and 24 females). Serum levels of chemerin, apelin, ICAM-1, E-selectin and hs-CRP were measured for obese and controls. RESULTS: Obese children showed higher levels of chemerin, apelin, ICAM-1 and E-selectin than controls. Chemerin and apelin showed significant correlations with all parameters except for age. Anthropometric parameters with hs-CRP revealed significant correlation even after adjustment for age and sex while apelin only showed a significant correlation with age. Multiple regression analyses with hs -CR , E-selectin and ICAM-1 as dependent variables and BMI Z score ,age, sex, chemerin and apelin as independent variables showed the effect of chemerin and apelin on the increased levels of hs -CR , E-selectin and ICAM-1 . CONCLUSION: Elevated levels of chemerin and apelin may serve as indices of ongoing obesity-related disorders in obese children.

A Comparative Study on Faecal Short-Chain Fatty Acids Concentration in Lean, Overweight and Obese School Children

The relationship between body weight and faecal short-chain acids (SCFAs) concentration may be interrelated and contribute to the development of childhood obesity and other metabolic diseases. This study aims to compare the faecal SCFAs concentration produced in lean, overweight and obese children aged 7 to 10 years old. Malay ethnic, healthy, lean, overweight and obese, age 7 to 10 years old from the selected primary school participated in this study.We assessed the socio-demographic and nutritional status of lean, overweight and obese children. A faecal sample was collected and analysed for faecal SCFAs concentration (acetic acid, butyric acid and propionic acid) by using the high-performance liquid chromatography (HPLC) method. A total of 42 overweight and obese children (n=22) and lean children (n=20) with mean age = 8.73 ± 1.03 years old; BMI = 33.51± 20.82 kg/m2; 50 % boys participated in the study. Intake of macronutrients was distributed evenly, but a substantial number of the participants did not achieve the RNI for energy and Malaysian Dietary Guidelines for Children and Adolescents (MDG) for carbohydrates and fibre intake. There was no significant difference between the group on dietary intakes (p&gt;0.05). The fecal SCFAs concentration of propionic acid (Mean=43.08 µmol/g; SD= 37.14) was the highest and followed by acetic acid (Mean= 29.73 µmol/g; SD= 23.30) and butyric acid (Mean= 23.19 µmol/g; SD= 17.75) with the overweight and obese children reported a higher concentration of butyrate (52%) and propionate (38%) as compared to lean children (p&gt;0.05). This data on faecal SCFAs concentration of overweight and obese among Malay school children had revealed the total faecal SCFAs being produced was 106.60 ± 63.83 µmol/g which is 34% higher than lean children. Despite the difference in trend found in faecal SCFAs concentration between lean, overweight and obese school children, this study had found the insignificant. Therefore, the underlying mechanisms that increased concentration of SCFAs concentration warrants in overweight and obese children future investigation in combating childhood obesity.

Gut Microbiota of Obese Children Influences Inflammatory Mucosal Immune Pathways in the Respiratory Tract to Influenza Virus Infection: Optimization of an Ideal Duration of Microbial Colonization in a Gnotobiotic Pig Model.

ABSTRACTThe impact of obesity on the human microbiota, immune maturation, and influenza virus infection has not been yet established in natural host animal models of influenza. In this study, gnotobiotic (Gn) pigs were colonized with human fecal microbiota (HFM) of obese (oHFM) or healthy lean (hHFM) children and infected at different periods (2-, 3-, and 5-weeks post-transplantation) using a zoonotic influenza virus strain. The infected oHFM pigs were characterized by lower levels of Firmicutes (Lactococcus, Lactobacillus, Turicibacter, and Streptococcus) and Actinobacteria (Bifidobacterium), which was associated with higher levels of Proteobacteria (Klebsiella), Bacteroidetes, and Verrucomicrobia (Akkermansia) compared with the infected hHFM group (P < 0.01). Furthermore, these genera significantly correlated with the expression of immune effectors, immune regulators, and inflammatory mediators, and displayed opposite trends between oHFM and hHFM groups (P < 0.01). The lymphoid and myeloid immune cell frequencies were differently modulated by the oHFM and hHFM colonization, especially apparent in the 5-weeks HFM colonized piglets. In addition, oHFM group had higher pro-inflammatory cytokines (IL-6, IL-12, TNF-α, and IFNγ) gene expression in the respiratory tract compared with the hHFM colonized pigs was detected. In conclusion, pigs colonized for longer duration, established oHFM increased the immune maturation favoring the activation of inflammatory mediators, however, the influenza virus load remained comparable with the hHFM group. Further, a longer duration of microbial colonization (5 weeks) may be required to reveal the impact of microbiome on the host immune maturation and susceptibility to influenza virus infection in the humanized Gn pig model.IMPORTANCE The diversity of gut microbiome of obese people differs markedly from that of lean healthy individuals which, in turn, influences the severity of inflammatory diseases because of differential maturation of immune system. The mouse model provides crucial insights into the mechanism(s) regulating the immune systems mediated by the gut microbiota but its applicability to humans is questionable because immune cells in mice are poorly activated in microbiota humanized mice. Several important strains of Bifidobacterium, Lactobacillus, and Clostridium fails to colonize the murine gut. Thus, understanding the role of certain important commensal gut bacterial species influences upon health and disease, a suitable large animal model like pig that supports the growth and colonization of most of the important human gut bacteria and possess comparable immunology and physiology to humans is beneficial to improve health.

Low leptin levels are associated with elevated physical activity among lean school children in rural Tanzania

BackgroundIn Sub-Saharan African countries, rapid urbanization and increasing socio-economic status are associated with a transition to decreased physical activity (PA). A more sedentary lifestyle is linked to increased body fat leading to increments in leptin levels. Since rodent and human studies in high-income countries have shown that starvation-induced hypoleptinemia triggers high PA, efforts are warranted to pursue the hypothesis that low leptin levels in lean children of low- and middle-income countries (LMIC) are also associated with high PA.MethodsIn this cross-sectional study, we assessed seven-day PA with triaxial accelerometry (ActiGraph GT3X) among 223 primary school children (9 to 12 years of age) in rural Tanzania. Moderate-to-vigorous PA (MVPA) and total accelerometer counts per day were outcome variables. Leptin was determined using enzyme linked immunosorbent assay tests from dried blood spots. Anthropometric assessments were conducted and food insecurity and socio-demographic data were gathered using semi-structured interviews.ResultsIn this sample of school children in rural Tanzania, leptin concentrations (median: 0.91 ng/mL, P25: 0.55, P75: 1.69), body mass index z-scores (median: -1.35, P25: -1.93, P75: -0.82), and height-for-age-z-scores (median: -1.16, P25: -1.96, P75: -0.61) were low. In contrast, PA levels were high with a median MVPA time of 119 min/day. Linear regression confirmed that leptin levels were negatively associated with MVPA (beta: -18.1; 95%CI: -29.7; -6.5; p = 0.002) and total accelerometer counts (beta: -90,256; 95%CI: -154,146; -26,365; p = 0.006). Children residing in areas with better infrastructure had lower MVPA levels (p < 0.001) and tended to have higher leptin levels (p = 0.062) than children residing in areas only reachable via dirt roads.ConclusionOur cross-sectional field study is the first that supports the hypothesis of low leptin levels as a potential endocrine trigger of high PA in lean children of a LMIC. We observed early signs of a PA transition towards a less active lifestyle in a subgroup residing in areas with better infrastructure that concomitantly tended to have higher leptin concentrations. Considering that area-dependent PA differences were more pronounced among girls than boys, whereas differences in leptin levels were less pronounced, not only biological, but also external factors explain PA transition.

Insulin resistance, leptin and adiponectin in lean and hypothyroid children and adolescents with obesity

BackgroundObesity usually complicates hypothyroidism. Adipokines like leptin and adiponectin secreted by adipose tissue modulate insulin resistance (IR), appetite, and obesity. The association between adipokines, IR, and thyroid hormone has not been sufficiently studied in children. We investigated leptin and adiponectin as well as IR and their association with thyroid hormone in both lean and hypothyroid children and adolescents with obesity.MethodsThe study included 30 lean hypothyroid, 30 hypothyroid children and adolescents with obesity, and 30 healthy lean children as the control group. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), fasting blood glucose, fasting insulin, homeostatic model assessment method of insulin resistance (HOMA-IR), leptin, and adiponectin levels were estimated in all participants.ResultsFasting insulin, HOMA-IR, and leptin levels were significantly elevated in hypothyroid children compared to the control group; more in hypothyroid children with obesity. In contrast, adiponectin levels were significantly lower in the hypothyroid children with obesity compared to the lean hypothyroid children and controls. HOMA-IR was positively correlated to TSH and BMI but inversely correlated with fT3 and fT4 in hypothyroid children. There was no correlation between IR and either leptin or adiponectin levels. Leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity.ConclusionInsulin resistance and leptin levels are increased in hypothyroid children and adolescents; more in those with obesity. IR is not related to leptin and adiponectin levels, however, leptin and adiponectin levels correlate well with BMI in hypothyroid children and adolescents with obesity.ImpactInsulin resistance (IR) and leptin levels increase in hypothyroid children and adolescent; more with obesity. IR is not related to leptin and adiponectin levels, however leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity.