The environmental obesogen tributyltin chloride acts via peroxisome proliferator activated receptor gamma to induce adipogenesis in murine 3T3-L1 preadipocytes

J Steroid Biochem Mol Biol. 2011 Oct;127(1-2):9-15. doi: 10.1016/j.jsbmb.2011.03.012. Epub 2011 Mar 21.

Abstract

Obesogens are chemicals that predispose exposed individuals to weight gain and obesity by increasing the number of fat cells, storage of fats into existing cells, altering metabolic rates, or disturbing the regulation of appetite and satiety. Tributyltin exposure causes differentiation of multipotent stromal stem cells (MSCs) into adipocytes; prenatal TBT exposure leads to epigenetic changes in the stem cell compartment that favor the production of adipocytes at the expense of bone, in vivo. While it is known that TBT acts through peroxisome proliferator activated receptor gamma to induce adipogenesis in MSCs, the data in 3T3-L1 preadipocytes are controversial. Here we show that TBT can activate the RXR-PPARγ heterodimer even in the presence of the PPARγ antagonist GW9662. We found that GW9662 has a 10-fold shorter half-life in cell culture than do PPARγ activators such as rosiglitazone (ROSI), accounting for previous observations that GW9662 did not inhibit TBT-mediated adipogenesis. When the culture conditions are adjusted to compensate for the short half-life of GW9662, we found that TBT induces adipogenesis, triglyceride storage and the expression of adipogenic marker genes in 3T3-L1 cells in a PPARγ-dependent manner. Our results are broadly applicable to the study of obesogen action and indicate that ligand stability is an important consideration in the design and interpretation of adipogenesis assays.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Adipogenesis / drug effects*
  • Anilides / pharmacology
  • Animals
  • Environmental Pollutants / toxicity*
  • Gene Expression / drug effects
  • Mice
  • PPAR gamma / agonists*
  • PPAR gamma / antagonists & inhibitors
  • Rosiglitazone
  • Thiazolidinediones / pharmacology
  • Trialkyltin Compounds / toxicity*
  • Triglycerides / metabolism

Substances

  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Environmental Pollutants
  • PPAR gamma
  • Thiazolidinediones
  • Trialkyltin Compounds
  • Triglycerides
  • Rosiglitazone
  • tributyltin