title: Exposure to p,p'-DDE enhances differentiation of 3T3-L1 preadipocytes in a model of sub-optimal differentiation.
abstract: The incidence of obesity is increasing worldwide at an alarming rate. Recently, exposure to environmental contaminants, especially organochlorines such as p,p'-dichlorodiphenyldichloroethylene (DDE), has been implicated as a possible causative factor in the increasing obesity epidemic. The objective of this study was to evaluate the ability of DDE to alter adipogenesis in a model of sub-optimal differentiation. 3T3-L1 preadipocytes were induced to differentiate in the presence of DDE (0.01-100μM) using a sub-optimal differentiation cocktail. Eight days after the initiation of differentiation, adipogenesis was assessed through neutral lipid staining, triglyceride accumulation, and expression of markers of terminal differentiation. Exposure to DDE induced a concentration dependent increase in intracellular neutral lipid accumulation as determined by Oil Red O staining and triglyceride assay. Alterations in lipid accumulation were accompanied by upregulation of genetic markers of differentiation. DDE (10μM) enhanced expression of fatty acid binding protein 4 and Sterol regulatory element-binding protein-1c at the 2.5 and 20μM concentrations. DDE (2.5, 10, and 20μM) induced upregulation of leptin and fatty acid synthase, as compared to sub-optimal vehicle control (0.05% ethanol). Our results indicate that DDE is capable of enhancing adipogenesis and intracellular lipid accumulation in 3T3-L1 cells through upregulation of molecular targets responsible for lipid storage.
authors.affiliation: Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
authors.forename: Lauren H
authors.initials: LH
authors.lastname: Mangum
authors.affiliation: Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Howell
authors.affiliation: Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA. Electronic address: chambers@cvm.msstate.edu.
authors.forename: Janice E
authors.initials: JE
authors.lastname: Chambers
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007306:Insecticides / Q000633:toxicity*; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D015415:Biomarkers; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D007306:Insecticides; D020738:Leptin; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D003633:Dichlorodiphenyl Dichloroethylene; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I
keywords: 3T3-L1; Adipogenesis; Organochlorine insecticides; p,p′-DDE