title: Low-Dose Bisphenol-A Impairs Adipogenesis and Generates Dysfunctional 3T3-L1 Adipocytes.
abstract: Environmental endocrine disruptors (EDCs), including bisphenol-A (BPA), have been recently involved in obesity and diabetes by dysregulating adipose tissue function. Our aim was to examine whether prolonged exposure to low doses of BPA could affect adipogenesis and adipocyte metabolic functions. Therefore, 3T3-L1 pre-adipocytes were cultured for three weeks with BPA 1 nM to mimic human environmental exposure. We evaluated BPA effect on cell proliferation, differentiation, gene expression and adipocyte metabolic function. BPA significantly increased pre-adipocyte proliferation (p<0.01). In 3T3-L1 adipocytes differentiated in the presence of BPA, the expression of Peroxisome proliferator-activated receptor gamma (PPARγ), Fatty Acid Binding Protein 4/Adipocyte Protein 2 (FABP4/AP2) and CCAAT/enhancer binding protein (C/EBPα) was increased by 3.5, 1.5 and 3 folds, respectively. Mature adipocytes also showed a significant increase in lipid accumulation (p<0.05) and alterations of insulin action, with significant reduction in insulin-stimulated glucose utilization (p<0.001). Moreover, in mature adipocytes, mRNA levels of Leptin, interleukin-6 (IL6) and interferon-γ (IFNγ) were significantly increased (p<0.05). In conclusion, BPA prolonged exposure at low doses, consistent with those found in the environment, may affect adipocyte differentiation program, enhancing pre-adipocyte proliferation and anticipating the expression of the master genes involved in lipid/glucose metabolism. The resulting adipocytes are hypertrophic, with impaired insulin signaling, reduced glucose utilization and increased pro-inflammatory cytokine expression. Thus, these data supported the hypothesis that BPA exposure, during critical stages of adipose tissue development, may cause adipocyte metabolic dysfunction and inflammation, thereby increasing the risk of developing obesity-related diseases.
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Ariemma
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.|URT Genomic of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Council of Research (CNR), via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: D'Esposito
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.|URT Genomic of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Council of Research (CNR), via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Liguoro
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Oriente
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Cabaro
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Liotti
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cimmino
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Longo
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.|URT Genomic of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Council of Research (CNR), via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Beguinot
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.|URT Genomic of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Council of Research (CNR), via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formisano
authors.affiliation: Department of Translational Medical Sciences, Federico II University of Naples, via S. Pansini, 5, 80131, Naples, Italy.|URT Genomic of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Council of Research (CNR), via S. Pansini, 5, 80131, Naples, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Valentino
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D066292:Lipid Droplets / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D005947:Glucose; D018836:Inflammation Mediators; D007328:Insulin; D010636:Phenols; D012333:RNA, Messenger; C006780:bisphenol A; D000098826:Bisphenol A Compounds