PPARγ‐dependent and PPARγ‐independent effects on the development of adipose cells from embryonic stem cells

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Abstract
Peroxisome proliferator‐activated receptor (PPAR) γ was shown to be required for adipocyte formation both in vivo and in vitro. However, the role of PPARγ in the initial steps of adipose cell development was not distinguished from its role in the terminal steps. We now show that PPARγ is expressed early in embryoid bodies (EBs) derived from embryonic stem cells and in E.8.5 mouse embryos. Addition of a specific ligand for PPARγ in developing EBs over‐expressing PPARγ did not commit stem cells towards the adipose lineage. In differentiated PPARγ−/− EBs, only markers characteristic of preadipocytes were found to be expressed. PPARδ is present in EBs but did not compensate for the lack of PPARγ in terminal differentiation. Taken together, these results favor a critical PPARγ‐independent phase culminating in preadipocyte formation that precedes a PPARγ‐dependent phase in the development of adipose cells from pluripotent stem cells.