Airborne Benzo[a]Pyrene may contribute to divergent Pheno-Endotypes in children

Background Asthma represents a syndrome for which our understanding of the molecular processes underlying discrete sub-diseases (i.e., endotypes), beyond atopic asthma, is limited. The public health needs to characterize etiology-associated endotype risks is becoming urgent. In particular, the roles of polyaromatic hydrocarbon (PAH), globally distributed combustion by-products, toward the two known endotypes – T helper 2 cell high (Th2) or T helper 2 cell low (non-Th2) – warrants clarification. Objectives To explain ambient B[a]P association with non-atopic asthma (i.e., a proxy of non-Th2 endotype) is markedly different from that with atopic asthma (i.e., a proxy for Th2-high endotype). Methods In a case-control study, we compare the non-atopic as well as atopic asthmatic boys and girls against their respective controls in terms of the ambient Benzo[a]pyrene concentration nearest to their home, plasma 15-Ft2-isoprostane (15-Ft2-isoP), urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), and lung function deficit. We repeated the analysis for i) dichotomous asthma outcome and ii) multinomial asthma—overweight/obese (OV/OB) combined outcomes. Results The non-atopic asthma cases are associated with a significantly higher median B[a]P (11.16 ng/m3) compared to that in the non-atopic controls (3.83 ng/m3; P-value < 0.001). In asthma-OV/OB stratified analysis, the non-atopic girls with lean and OV/OB asthma are associated with a step-wisely elevated B[a]P (median,11.16 and 18.00 ng/m3, respectively), compared to the non-atopic lean control girls (median, 4.28 ng/m3, P-value < 0.001). In contrast, atopic asthmatic children (2.73 ng/m3) are not associated with a significantly elevated median B[a]P, compared to the atopic control children (2.60 ng/m3; P-value > 0.05). Based on the logistic regression model, on ln-unit increate in B[a]P is associated with 4.7-times greater odds (95% CI, 1.9–11.5, P = 0.001) of asthma among the non-atopic boys. The same unit increase in B[a]P is associated with 44.8-times greater odds (95% CI, 4.7–428.2, P = 0.001) among the non-atopic girls after adjusting for urinary Cotinine, lung function deficit, 15-Ft2-isoP, and 8-oxodG. Conclusions Ambient B[a]P is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among lean children. Furthermore, lung function deficit, 15-Ft2-isoP, and 8-oxodG are associated with profound alteration of B[a]P-asthma associations among the non-atopic children.

Determining the effects of excess weight on renal cortical stiffness in children and adolescents with point Shear Wave Elastography

Aim: To determine the early effects of excess weight on renal cortical stiffness in children and adolescents using point shear wave elastography (pSWE). Materials and methods: One hundred and forty-six overweight and obese children (43.2% male; mean age, 12.6±2.9 years: range 4.3-18) and 48 lean children (27.1% male: mean age, 12.4±3.4: range 4.8-18.9) were included in the study and control group, respectively. pSWE measurements of the two kidneys were performed. The mean value of shear wave velocity was compared between groups. Results: The mean shear wave velocity was 2.79±0.53 m/s for the control subjects and 3.09±0.59 m/s for the overweight-obese subjects. The differences between the two groups were sta-tistically significant (p=0.001). There was no correlation between shear wave velocity and age or depth. A positive correlation was found between shear wave velocity and body mass index, body mass index-standard deviation score. Conclusion: Renal cortical stiffness was higher in children with excess weight than in lean children. This study is the first attempt at applying pSWE to investigate the early adverse effects of excess weight.

CD36 and GPR120 Methylation Associates with Orosensory Detection Thresholds for Fat and Bitter in Algerian Young Obese Children

Background: The spontaneous preference for dietary fat is regulated by two lingual lipid sensors (CD36 and GPR120) in humans and rodents. Our objective was to investigate whether obesity in children is associated with methylation of lipid sensor genes, and whether this alteration was implicated in altered gustatory perception of fat and bitter and increased preference of palatable foods. Methods: School children were recruited and classified according to their body mass index (BMI) z-score into two groups: obese and lean children. The detection of orosensory perception for oleic acid and 6-n-propylthiouracil was assessed by using a 3-alternative forced-choice test. After blood DNA extraction, methylation patterns were investigated by methylation-specific PCR. The children were also subjected to a food habit questionnaire. Results: Obese children showed higher lipid and bitter detection thresholds than lean children. Besides, more obese children presented higher methylation level of the CpG sites than lean participants. Interestingly, CD36 and GPR120 gene methylation was associated with high lipid detection thresholds in obese participants. The obese participants preferred highly palatable fat-rich food items, associated with CD36 and GPR120 gene methylation. Conclusion: Epigenetic changes in CD36 and GPR120 genes might contribute to low orosensory perception of fat and bitter taste, and might be, consequently, critically involved in obesity in children

Association of the 3′UTR polymorphism (rs11665896) in the FGF21 gene with metabolic status and nutrient intake in children with obesity

Background Fibroblast growth factor 21 (FGF21) is considered an important regulator of lipid and glucose metabolism. However, the role of FGF21 in macronutrient intake and metabolic disease, particularly in pediatric population, still needs further clarification. This study aimed to evaluate the association of rs11665896 in the FGF21 gene with metabolic status and macronutrient intake in a cohort of Mexican children with obesity. Methods Eighty-four lean children and 113 children with obesity, from 8 to 11 years of age, were recruited. FGF21 rs11665896 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Somatometric evaluations, nutrient intake, glucose, lipids, insulin and FGF21 serum levels were measured in the obesity group. Results The T allele of rs11665896 in the FGF21 gene was associated with obesity (odds ratio [OR] = 1.99, 95% confidence interval [CI] = 1.14–3.46; p = 0.0151). Subjects with obesity carrying the TT genotype consumed less lipids and more carbohydrates compared to other genotypes. Circulating FGF21 levels correlated negatively with carbohydrate intake (r = −0.232, p = 0.022) and positively with body weight (r = 0.269, p = 0.007), waist (r = 0.242, p = 0.016) and hip girth (r = 0.204, p = 0.042). FGF21 levels were lower in carriers of at least one T allele. Conclusions Genetic variants in FGF21 could influence metabolic status, food preferences and qualitative changes in nutritional behavior in children.

Fatty pancreas in relation to insulin resistance and metabolic syndrome in children with obesity

Background Ectopic visceral fat is a major risk factor for obesity complications including insulin resistance and metabolic syndrome. Ultrasonography is a simple bedside screening tool used for the assessment of ectopic visceral fat including fatty pancreas. This study investigates the association between insulin resistance, metabolic syndrome and fatty pancreas detected by ultrasound in children with obesity. Methods This case-control study included 50 prepubertal obese (body mass index [BMI] ≥95th age- and sex-specific percentiles) and 30 lean children (BMI 5th–85th age- and sex-specific percentiles) as the control group. Clinical and laboratory parameters of metabolic syndrome including anthropometric indices of central obesity, blood pressure, fasting glucose and lipid profile were measured. Homeostasis model assessment-insulin resistance (HOMA-IR) was used to assess insulin resistance. Ultrasonographic assessment for pancreatic fat was done for all children. Results Fifty-eight percent of obese children had fatty pancreas. Obese children with fatty pancreas had a higher rate of metabolic syndrome (p=0.013) and insulin resistance than those with non-fatty pancreas (p=0.012). Regression analysis revealed that fatty pancreas is an independent predictor of metabolic syndrome and insulin resistance. Fatty pancreas increases the risk for metabolic syndrome (odds ratio [OR] 11.40; 95% confidence interval [CI]: 2.69–48.22) and insulin resistance (OR 7.85; 95% CI: 2.20–28.05) in children with obesity. Conclusions Obese children have higher pancreatic fat accumulation than lean children. Obese children with fatty pancreas are more susceptible to insulin resistance and metabolic syndrome.