Exposure to p,p'-DDE Enhances Differentiation of 3T3-L1 Preadipocytes in a Model of Sub-Optimal Differentiation

Toxicol Lett. 2015 Oct 14;238(2):65-71. doi: 10.1016/j.toxlet.2015.07.009. Epub 2015 Jul 19.

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.

Keywords: 3T3-L1; Adipogenesis; Organochlorine insecticides; p,p′-DDE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Biomarkers / metabolism
  • Dichlorodiphenyl Dichloroethylene / toxicity*
  • Dose-Response Relationship, Drug
  • Fatty Acid Synthase, Type I / genetics
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Insecticides / toxicity*
  • Leptin / genetics
  • Leptin / metabolism
  • Mice
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Time Factors
  • Triglycerides / metabolism

Substances

  • Biomarkers
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • Insecticides
  • Leptin
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Dichlorodiphenyl Dichloroethylene
  • FASN protein, human
  • Fatty Acid Synthase, Type I