PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation

P. Hallenborg, R. K. Petersen, Søren Feddersen, U. Sundekilde, J. B. Hansen, B. Blagoev, L. Madsen, K. Kristiansen

Research output: Contribution to journalJournal articleResearchpeer-review


Adipocyte differentiation is orchestrated by the ligand-activated nuclear receptor PPARγ. Endogenous ligands comprise oxidized derivatives of arachidonic acid and structurally similar PUFAs. Although expression of PPARγpeaks in mature adipocytes, ligands are produced primarily at the onset of differentiation. Concomitant with agonist production, murine fibroblasts undergo two rounds of mitosis referred to as mitotic clonal expansion. Here we show that mouse embryonic fi broblasts deficient in either of two cell cycle inhibitors, the transcription factor p53 or its target gene encoding the cyclindependent kinase inhibitor p21, exhibit increased adipogenic potential. The antiadipogenic effect of p53 relied on its transcriptional activity and p21 expression but was circumvented by administration of an exogenous PPARγ agonist suggesting a linkage between cell cycling and PPARγ ligand production. Indeed, cell cycle inhibitory compounds decreased PPARγligand production in differentiating 3T3-L1 preadipocytes. Furthermore, these inhibitors abolished the release of arachidonic acid induced by the hormonal cocktail initiating adipogenesis. Collectively, our results suggest that murine fibroblasts require clonal expansion for PPARγligand production at the onset of adipocyte differentiation.

Original languageEnglish
JournalJournal of Lipid Research
Issue number12
Pages (from-to)2491-2500
Publication statusPublished - 2014


  • Adipocytes
  • Arachidonic acid
  • Cell cycling
  • Nuclear receptors/lipid ligands
  • Peroxisome proliferator-activated receptor
  • Transcription


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