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

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 PPAR gamma 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, PPAR gamma promoter activation and PPAR gamma l, PPAR gamma 2, Pref-1 and SOX9 expression. Depending on the exposure window, TBT promoted subsequent adipogenesis independently and dependently from PPAR gamma. In undifferentiated MSC, TBT exposure induced a transcriptional PPAR gamma-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 PPAR gamma 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. (c) 2014 Elsevier Ireland Ltd. All rights reserved.