Obesogenic effects of chlorpyrifos and its metabolites during the differentiation of 3T3-L1 preadipocytes

Food Chem Toxicol. 2020 Mar;137:111171. doi: 10.1016/j.fct.2020.111171. Epub 2020 Feb 1.

Abstract

Chlorpyrifos (CPF) is an organophosphorus pesticide widely and extensively used in agriculture in more than one hundred countries and found ubiquitously in the environment. The present study was aimed at providing a better understanding of the obesogenic potential of CPF and its metabolites, as well as to evaluate their effects on the adipocyte differentiation process. For it, during the initial differentiation process, 3T3-L1 mouse preadipocytes were exposed to different concentrations of CPF, CPF-oxon (CPO), or 3,5,6-trichloropyridinol (TCP), which did not affect cell survival. Results showed how CPF and, to a lesser extent, its metabolite TCP, had a positive metabolic influence over the adipogenic process by fostering an increase in the number of differentiated 3T3-L1 preadipocytes, and by enhancing the capacity to store lipid droplets. These processes seem to occur through the upregulation of the transcription factors CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which are related to a significant higher expression of the fatty acid-binding protein 4 (FABP4) adipokine. Based on this finding, CPF exposure could be one of the many factors that contributes to the worldwide increase in the incidence of obesity. However, additional investigations are clearly needed.

Keywords: Adipogenesis; Chlorpyrifos; Obesogen; Peroxisome proliferator-activated receptor γ.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipogenesis / drug effects*
  • Animals
  • Cell Differentiation / drug effects*
  • Cell Survival / drug effects
  • Chlorpyrifos / analogs & derivatives
  • Chlorpyrifos / toxicity*
  • Endocrine Disruptors / toxicity*
  • Insecticides / toxicity*
  • Lipid Droplets / metabolism
  • Mice
  • Obesity / chemically induced
  • Pyridones / toxicity

Substances

  • Endocrine Disruptors
  • Insecticides
  • Pyridones
  • O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate
  • 3,5,6-trichloro-2-pyridinol
  • Chlorpyrifos