title: Bisphenol-A impairs insulin action and up-regulates inflammatory pathways in human subcutaneous adipocytes and 3T3-L1 cells.
abstract: Current evidence indicates that chemical pollutants may interfere with the homeostatic control of nutrient metabolism, thereby contributing to the increased prevalence of metabolic disorders. Bisphenol-A (BPA) is a lipophilic compound contained in plastic which is considered a candidate for impairing energy and glucose metabolism. We have investigated the impact of low doses of BPA on adipocyte metabolic functions. Human adipocytes derived from subcutaneous adipose tissue and differentiated 3T3-L1 cells were incubated with BPA, in order to evaluate the effect on glucose utilization, insulin sensitivity and cytokine secretion. Treatment with 1 nM BPA significantly inhibited insulin-stimulated glucose utilization, without grossly interfering with adipocyte differentiation. Accordingly, mRNA levels of the adipogenic markers PPARγ and GLUT4 were unchanged upon BPA exposure. BPA treatment also impaired insulin-activated receptor phosphorylation and signaling. Moreover, adipocyte incubation with BPA was accompanied by increased release of IL-6 and IFN-γ, as assessed by multiplex ELISA assays, and by activation of JNK, STAT3 and NFkB pathways. Treatment of the cells with the JNK inhibitor SP600125 almost fully reverted BPA effect on insulin signaling and glucose utilization. In conclusion, low doses of BPA interfere with inflammatory/insulin signaling pathways, leading to impairment of adipose cell function.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Valentino
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: D'Esposito
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy ; Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Salerno, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Passaretti
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy ; Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Salerno, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Liotti
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Cabaro
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Longo
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perruolo
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Oriente
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy ; Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Beguinot
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS-CNR), Naples, Italy ; Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II", Naples, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formisano
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D007328:Insulin / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D050151:Subcutaneous Fat / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D005947:Glucose; D007328:Insulin; D048031:JNK Mitogen-Activated Protein Kinases; D020738:Leptin; D016328:NF-kappa B; D010636:Phenols; D012333:RNA, Messenger; D011972:Receptor, Insulin; D050796:STAT3 Transcription Factor; C006780:bisphenol A; D000098826:Bisphenol A Compounds