| First Author | Hallenborg P | Year | 2014 |
| Journal | J Lipid Res | Volume | 55 |
| Issue | 12 | Pages | 2491-500 |
| PubMed ID | 25312885 | Mgi Jnum | J:217167 |
| Mgi Id | MGI:5613271 | Doi | 10.1194/jlr.M050658 |
| Citation | Hallenborg P, et al. (2014) PPARgamma ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation. J Lipid Res 55(12):2491-500 |
| abstractText | Adipocyte differentiation is orchestrated by the ligand-activated nuclear receptor PPARgamma. Endogenous ligands comprise oxidized derivatives of arachidonic acid and structurally similar PUFAs. Although expression of PPARgamma peaks 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 fibroblasts deficient in either of two cell cycle inhibitors, the transcription factor p53 or its target gene encoding the cyclin-dependent 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 PPARgamma agonist suggesting a linkage between cell cycling and PPARgamma ligand production. Indeed, cell cycle inhibitory compounds decreased PPARgamma ligand 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 PPARgamma ligand production at the onset of adipocyte differentiation. |
