Potential role of aryl hydrocarbon receptor signaling in childhood obesity.

There is a growing concern that junk food has contributed to the childhood obesity epidemic. Recently, experimental studies suggested that the aryl hydrocarbon receptor (AHR) gene is strongly linked to western diet-induced obesity. This study investigated the potential role of AHR signaling in childhood obesity and the possible associations of the AHR-aryl hydrocarbon receptor repressor (AHRR)-cytochrome P450 1B1 (CYP1B1) axis with fatty acid homeostasis and the appetite-related hormones, leptin and ghrelin. The study included 80 children; 54 obese and 26 non-obese of matched age and sex. Demographic data, anthropometric measurements, and lipid profile were assessed. Expression of AHR signaling genes was analyzed in blood cells by qRT-PCR. Serum insulin, leptin and ghrelin levels were measured using ELISA. The statistical power of this study, calculated using G*Power version 3.1.9.2, was 90% (α = 0.05). AHR and CYP1B1 gene expression levels were upregulated in the obese group compared to controls, whereas AHRR, stearoyl-CoA desaturase 1 (SCD1), and peroxisome proliferator-activated receptor-γ2 (PPARγ2) were downregulated. Serum leptin correlated positively, while serum ghrelin correlated negatively with both AHR and CYP1B1. Stratification of obese children by age revealed more activated AHR signaling in younger than in older children. Receiver-operating-characteristic (ROC) analysis revealed that AHR, AHRR and CYP1B1 could discriminate between obese and normal weight children. Multivariate analysis showed that AHRR, CYP1B1 and ghrelin could be significant independent predictors of obesity. This study provides new insights into the molecular mechanisms contributing to childhood obesity by revealing alterations in the AHR-AHRR-CYP1B1 axis, which could serve as a promising therapeutic target for childhood obesity. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Nancy N Shahin, Ghada T Abd-Elwahab, Afaf A Tawfiq, Hanan M Abdelgawad. Potential role of aryl hydrocarbon receptor signaling in childhood obesity. Biochimica et biophysica acta. Molecular and cell biology of lipids. 2020 Aug;1865(8):158714

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PMID: 32302739

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