Tributyltin affects adipogenic cell fate commitment in mesenchymal stem cells by a PPARγ independent mechanism

Chem Biol Interact. 2014 May 5;214:1-9. doi: 10.1016/j.cbi.2014.01.021. Epub 2014 Feb 8.

Abstract

The food contaminant tributyltin (TBT) is an endocrine disrupting compound (EDC) promoting adipogenic differentiation in vitro and in vivo. Although prenatal TBT exposure has been shown to induce obesity, the underlying mechanisms and the role of the transcription factor PPARγ are not clarified yet. At different stages of adipogenesis, multipotent murine mesenchymal stem cells (MSC), C3H10T1/2, were exposed to TBT and analyzed for adipogenic differentiation, PPARγ promoter activation and PPARγ1, PPARγ2, Pref-1 and SOX9 expression. Depending on the exposure window, TBT promoted subsequent adipogenesis independently and dependently from PPARγ. In undifferentiated MSC, TBT exposure induced a transcriptional PPARγ-independent repression of Pref-1 and SOX9, which are both suppressors of adipogenic cell fate commitment. During hormonal induction TBT additionally enhanced adipogenic differentiation by PPARγ signaling. The impact of TBT on early cell fate development documents a novel mechanistic insight in the development of adipocytes derived from MSC and its susceptibility to EDC.

Keywords: Adipogenesis; EDC; Mesenchymal stem cells; PPARγ; TBT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Animals
  • Blotting, Western
  • Cell Differentiation
  • Cell Line
  • Cell Lineage
  • Genetic Markers
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Trialkyltin Compounds / pharmacology*

Substances

  • Genetic Markers
  • PPAR gamma
  • Trialkyltin Compounds
  • tributyltin