title: Tributyltin differentially promotes development of a phenotypically distinct adipocyte.
abstract: OBJECTIVE
  Environmental endocrine disrupting chemicals (EDCs) are increasingly implicated in the pathogenesis of obesity. Evidence implicates various EDCs as being proadipogenic, including tributyltin (TBT), which activates the peroxisome proliferator activated receptor-γ (PPARγ). However, the conditions required for TBT-induced adipogenesis and its functional consequences are incompletely known.
  
  
  METHODS
  The costimulatory conditions necessary for preadipocyte-to-adipocyte differentiation were compared between TBT and the pharmacological PPARγ agonist troglitazone (Trog) in the 3T3-L1 cell line; basal and insulin-stimulated glucose uptake were assessed using radiolabeled 2-deoxyglucose.
  
  
  RESULTS
  TBT enhanced expression of the adipocyte marker C/EBPα with coexposure to either isobutylmethylxanthine or insulin in the absence of other adipogenic stimuli. Examination of several adipocyte-specific proteins revealed that TBT and Trog differentially affected protein expression despite comparable PPARγ stimulation. In particular, TBT reduced adiponectin expression upon maximal adipogenic stimulation. Under submaximal stimulation, TBT and Trog differentially promoted adipocyte-specific gene expression despite similar lipid accumulation. Moreover, TBT attenuated Trog-induced adipocyte gene expression under conditions of cotreatment. Finally, TBT-induced adipocytes exhibited altered glucose metabolism, with increased basal glucose uptake.
  
  
  CONCLUSIONS
  TBT-induced adipocytes are functionally distinct from those generated by a pharmacological PPARγ agonist, suggesting that obesogen-induced adipogenesis may generate dysfunctional adipocytes with the capacity to deleteriously affect global energy homeostasis.
authors.affiliation: Committee on Molecular Metabolism and Nutrition, University of Chicago, Illinois, USA.|Pritzker School of Medicine, University of Chicago, Illinois, USA.
authors.forename: Shane M
authors.initials: SM
authors.lastname: Regnier
authors.affiliation: Kovler Diabetes Center, University of Chicago, Illinois, USA.|Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Illinois, USA.
authors.forename: Essam
authors.initials: E
authors.lastname: El-Hashani
authors.affiliation: Kovler Diabetes Center, University of Chicago, Illinois, USA.|Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Illinois, USA.
authors.forename: Wakanene
authors.initials: W
authors.lastname: Kamau
authors.affiliation: Kovler Diabetes Center, University of Chicago, Illinois, USA.|Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Illinois, USA.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Kovler Diabetes Center, University of Chicago, Illinois, USA.|Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Illinois, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Massad
authors.affiliation: Committee on Molecular Metabolism and Nutrition, University of Chicago, Illinois, USA.|Pritzker School of Medicine, University of Chicago, Illinois, USA.|Kovler Diabetes Center, University of Chicago, Illinois, USA.|Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Illinois, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sargis
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D015870:Gene Expression; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D010641:Phenotype; D014220:Trialkyltin Compounds / Q000378:metabolism*
chemical_list: D047495:PPAR gamma; D014220:Trialkyltin Compounds; C011559:tributyltin