Menale Ciro, Piccolo Maria Teresa, Cirillo Grazia, Calogero Raffaele A, Papparella Alfonso, Mita Luigi, Del Giudice Emanuele Miraglia, Diano Nadia, Crispi Stefania, Mita Damiano Gustavo
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.
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.
J Mol Endocrinol. 2015 Jun;54(3):289-303. doi: 10.1530/JME-14-0282. Epub 2015 Apr 15.
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.
双酚A（BPA）是一种外源性内分泌干扰化学物质。体外和体内研究表明，BPA会改变脂肪组织中的内分泌代谢途径，从而增加代谢紊乱和肥胖的风险。BPA可通过调节直接参与代谢稳态和肥胖的基因表达来影响脂肪组织，并增加脂肪细胞数量或大小。在动物模型中进行的多项研究证实了BPA具有致肥胖作用，但其对人类脂肪细胞的影响，尤其是对儿童脂肪细胞的影响，尚未得到充分研究。本研究的目的是了解环境相关剂量的BPA干扰调节青春期前非肥胖儿童成熟人类脂肪细胞代谢的经典内分泌功能的分子机制。根据生理环境的不同，BPA可作为雌激素激动剂或拮抗剂。为了确定与代谢相关的分子特征，通过微阵列分析评估了暴露于雌激素的青春期前儿童成熟脂肪细胞的转录修饰。对与代谢紊乱相关的失调基因进行分析，使我们能够识别出一小部分基因，它们的表达方式与用BPA处理的脂肪细胞相反。具体而言，我们发现BPA会增加促炎细胞因子的表达以及FABP4和CD36的表达，这两个基因参与脂质代谢。此外，BPA会降低参与胰岛素产生的基因PCSK1的表达。这些结果表明，接触BPA可能是导致涉及儿童代谢失调的代谢紊乱的一个重要危险因素。
