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Related Experiment Videos

Differential activation of adipogenesis by multiple PPAR isoforms

R P Brun1, P Tontonoz, B M Forman

  • 1Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Genes & Development
|April 15, 1996
PubMed
Summary

Peroxisome proliferator-activated receptor gamma (PPARgamma) is the main driver of adipogenesis, significantly inducing fat cell differentiation. PPARalpha shows some adipogenic potential, while PPARdelta does not stimulate this process.

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) is a key nuclear receptor in adipose tissue, regulating adipocyte gene expression and differentiation.
  • Three PPAR isoforms exist: PPARgamma, PPARalpha, and PPARdelta, with varying expression levels in adipose depots.

Purpose of the Study:

  • To directly compare the adipogenic potential of PPARgamma, PPARalpha, and PPARdelta.
  • To investigate the molecular mechanisms underlying the differential adipogenic activities of PPAR isoforms.

Main Methods:

  • Ectopic expression of PPAR isoforms in cells.
  • Assessment of adipogenesis at morphological and molecular levels.
  • Analysis of PPAR isoform binding to DNA response elements (ARE6, ARE7).

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  • Examination of cooperation between PPARgamma and C/EBPalpha.

    • Main Results:

    • PPARgamma powerfully induced adipogenesis in response to activators.
    • PPARalpha exhibited less adipogenic potential but could induce differentiation with strong activators.
    • PPARdelta did not stimulate adipogenesis.
    • PPARgamma preferentially bound to specific DNA response sequences (ARE6, ARE7) compared to PPARalpha and PPARdelta.
    • Only PPARgamma cooperated with C/EBPalpha in promoting adipogenesis.

    Conclusions:

    • PPARgamma is the predominant receptor regulating adipogenesis.
    • PPARalpha may contribute to adipogenesis in specific adipose depots or disease states.
    • Differential DNA-binding affinities contribute to the distinct roles of PPAR isoforms in adipogenesis.