title: Bisphenol A enhances adipogenic differentiation of human adipose stromal/stem cells.
abstract: Exposure of humans to the endocrine disrupter bisphenol A (BPA) has been associated with increased weight and obesity. However, the mechanism(s) by which BPA increases adipose tissue in humans remains to be determined. The goal of this study was to determine the effects of BPA on adipogenesis of cultured human adipose stromal/stem cells (ASCs), precursors to mature adipocytes. ASCs from three donors were cultured for either 14 or 21 days in adipogenic differentiation media containing increasing concentrations of BPA (100 pM-10 μM). The extent of adipogenic differentiation in the ASCs was assessed by staining with Oil Red O to visualize adipogenic differentiation and then quantified by extraction and optical density measurement of the retained dye. BPA significantly enhanced adipogenesis at a concentration of 1 μM after 21 days of culture. Additionally, we found that BPA increased transcription of the estrogen receptor (ER (ESR1)) and that treatment with the ER antagonist ICI 182 780, blocked the effects of BPA, indicating that BPA may act via an ER-mediated pathway. The results of molecular analyses indicated that the expression of the adipogenesis-associated genes dual leucine zipper-bearing kinase (DLK (MAP3K12)), IGF1, CCAAT/enhancer-binding protein alpha (C/EBPα (CEBPA)), peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), and lipoprotein lipase (LPL) was temporally accelerated and increased by BPA. In summary, these results indicate that BPA significantly enhances adipogenesis in ASCs through an ER-mediated pathway at physiologically relevant concentrations.
authors.affiliation: Center for Stem Cell Research and Regenerative MedicineTulane University School of Medicine, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USASection of Hematology and Medical OncologyDepartment of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USADepartment of PharmacologyTulane University School of Medicine, New Orleans, Louisiana 70112, USA.
authors.forename: Jason F
authors.initials: JF
authors.lastname: Ohlstein
authors.affiliation: Center for Stem Cell Research and Regenerative MedicineTulane University School of Medicine, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USASection of Hematology and Medical OncologyDepartment of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USADepartment of PharmacologyTulane University School of Medicine, New Orleans, Louisiana 70112, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Strong
authors.affiliation: Center for Stem Cell Research and Regenerative MedicineTulane University School of Medicine, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USASection of Hematology and Medical OncologyDepartment of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USADepartment of PharmacologyTulane University School of Medicine, New Orleans, Louisiana 70112, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: McLachlan
authors.affiliation: Center for Stem Cell Research and Regenerative MedicineTulane University School of Medicine, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USASection of Hematology and Medical OncologyDepartment of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USADepartment of PharmacologyTulane University School of Medicine, New Orleans, Louisiana 70112, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.affiliation: Center for Stem Cell Research and Regenerative MedicineTulane University School of Medicine, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USASection of Hematology and Medical OncologyDepartment of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USADepartment of PharmacologyTulane University School of Medicine, New Orleans, Louisiana 70112, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Burow
authors.affiliation: Center for Stem Cell Research and Regenerative MedicineTulane University School of Medicine, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USASection of Hematology and Medical OncologyDepartment of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USADepartment of PharmacologyTulane University School of Medicine, New Orleans, Louisiana 70112, USA Center for Stem Cell Research and Regenerative MedicineTulane University School of Medicine, 1430 Tulane Avenue, SL-99, New Orleans, Louisiana 70112, USASection of Hematology and Medical OncologyDepartment of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USADepartment of PharmacologyTulane University School of Medicine, New Orleans, Louisiana 70112, USA bbunnell@tulane.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects*; D000328:Adult; D053687:Adult Stem Cells / Q000187:drug effects* / Q000502:physiology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008875:Middle Aged; D010636:Phenols / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: adipogenesis; adipose stromal/stem cell; bisphenol A (BPA); endocrine disrupters; estrogen receptor