title: Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders.
abstract: Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical. In vitro and in vivo studies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating the expression of the genes that are directly involved in metabolic homeostasis and obesity. Several studies performed in animal models have accounted for an obesogen role of BPA, but its effects on human adipocytes - especially in children - have been poorly investigated. The aim of this study is to understand the molecular mechanisms by which environmentally relevant doses of BPA can interfere with the canonical endocrine function that regulates metabolism in mature human adipocytes from prepubertal, non-obese children. BPA can act as an estrogen agonist or antagonist depending on the physiological context. To identify the molecular signatures associated with metabolism, transcriptional modifications of mature adipocytes from prepubertal children exposed to estrogen were evaluated by means of microarray analysis. The analysis of deregulated genes associated with metabolic disorders allowed us to identify a small group of genes that are expressed in an opposite manner from that of adipocytes treated with BPA. In particular, we found that BPA increases the expression of pro-inflammatory cytokines and the expression of FABP4 and CD36, two genes involved in lipid metabolism. In addition, BPA decreases the expression of PCSK1, a gene involved in insulin production. These results indicate that exposure to BPA may be an important risk factor for developing metabolic disorders that are involved in childhood metabolism dysregulation.
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Ciro
authors: C
authors: Menale
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Maria Teresa
authors: MT
authors: Piccolo
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Grazia
authors: G
authors: Cirillo
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Raffaele A
authors: RA
authors: Calogero
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Alfonso
authors: A
authors: Papparella
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Luigi
authors: L
authors: Mita
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Emanuele Miraglia
authors: EM
authors: Del Giudice
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Nadia
authors: N
authors: Diano
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy stefania.crispi@ibbr.cnr.it.
authors: Stefania
authors: S
authors: Crispi
authors: Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy Department of Experimental MedicineSecond University of Naples, Via S. Maria di Costantinopoli 16, 80138 Naples, ItalyNational Laboratory of Endocrine DisruptorsINBB, Via P. Castellino 111, 80131 Naples, ItalyGene Expression and Molecular Genetics LaboratoryIBBR - CNR, UOS Napoli Via P. Castellino 111, 80131 Naples, ItalyDepartment of WomanChild and General and Specialized Surgery, Second University of Naples, Via Luigi De Crecchio 4, 80138 Naples, ItalyBioinformatics and Genomics UnitMBC Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, ItalyBiophysics LaboratoryIGB - CNR, Via P. Castellino 111, 80131 Naples, Italy.
authors: Damiano Gustavo
authors: DG
authors: Mita
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002478:Cells, Cultured; D002648:Child; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D000078790:Insulin Secretion; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008659:Metabolic Diseases / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000633:toxicity*; D059467:Transcriptome / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004958:Estradiol; D007328:Insulin; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: adipocytes; bisphenol A; children; gene expression; metabolic homeostasis