Project description:Bisphenol A (BPA) is a xenobiotic endocrine disrupting chemical. In vitro and in vivo studies indicated that BPA alters endocrine-metabolic pathways in adipose tissue increasing the risk of developing metabolic disorders. BPA effects on human adipocytes, specifically in children, are poorly investigated. To investigate in childhood the effect of exposure to BPA on metabolic disorders we analyzed in vitro the effects of environmentally relevant doses of BPA on gene expression of mature human adipocytes from pre-pubertal lean patients and on related physiological outcomes. Adipocytes from children were treated in vitro with BPA and gene expression was evaluated by qRT-PCR. Genome wide analyses were performed using GeneChip Human Gene 1.0 ST array. Lipid content in adipocytes was estimated by ORO staining and Triglyceride Quantification Kit. Secreted IL-1beta, in adipocytes culture medium, and insulin, in PANC-1 culture medium, were performed using ELISA assays. BPA was found to promote up-regulation of ER? and ERR?, and down-regulation of GPR30 expression modulating estrogen signaling and following a non-linear dose-response. Microarray data analysis demonstrated that BPA increases the gene expression of pro-inflammatory cytokines and lipid metabolism-related FABP4 and CD36 in adipocytes. PCSK1 resulted the most interesting gene being down-regulated by BPA thus impairing insulin production in pancreas. BPA promotes inflammation and lipid metabolism dysregulation in adipocytes from lean children. Moreover, PCSK1 can be a key gene in BPA action modulating insulin production. Exposure to BPA in childhood may be an important risk factor in developing obesity and metabolic disorders. Three prototypic situations were analyzed (5 replication each): untreated cells (C), 10 nM BPA treated cells (BPA), 1 nM 17-beta Estradiol treated cells (ES).
