Glyphosate Inhibits PPAR Gamma Induction and Differentiation of Preadipocytes and is able to Induce Oxidative Stress

J Biochem Mol Toxicol. 2016 Aug;30(8):404-13. doi: 10.1002/jbt.21804. Epub 2016 Apr 4.

Abstract

Glyphosate-based herbicides (GF) are extensively used for weed control. Thus, it is important to investigate their putative toxic effects. We have reported that GF at subagriculture concentrations inhibits proliferation and differentiation to adipocytes of 3T3-L1 fibroblasts. In this investigation, we evaluated the effect of GF on genes upregulated during adipogenesis. GF was able to inhibit the induction of PPAR gamma, the master gene in adipogenesis but not C/EBP beta, which precedes PPAR gamma activation. GF also inhibited differentiation and proliferation of another model of preadipocyte: mouse embryonic fibroblasts. In exponentially growing 3T3-L1 cells, GF increased lipid peroxidation and the activity of the antioxidant enzyme, superoxide dismutase. We also found that proliferation was inhibited with lower concentrations of GF when time of exposure was extended. Thus, GF was able to inhibit proliferation and differentiation of preadipocytes and to induce oxidative stress, which is indicative of its ability to alter cellular physiology.

Keywords: 3T3-L1 Fibroblasts; Differentiation; Glyphosate Based-Herbicide; MEFs; Oxidative Stress.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Embryo, Mammalian
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Glyphosate
  • Herbicides / pharmacology*
  • Lipid Peroxidation / drug effects
  • Mice
  • Oxidative Stress
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Primary Cell Culture
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • CEBPB protein, human
  • Herbicides
  • PPAR gamma
  • Superoxide Dismutase
  • Glycine