Article open access publication

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

The Journal of Lipid Research, American Society for Biochemistry & Molecular Biology (ASBMB), ISSN 0022-2275

Volume 55, 12, 2014

DOI:10.1194/jlr.m050658, Dimensions: pub.1046632018, PMC: PMC4242442, PMID: 25312885,

Affiliations

Organisations

  1. (1) University of Southern Denmark, grid.10825.3e, SDU
  2. (2) University of Copenhagen, grid.5254.6, KU
  3. (3) National Institute of Nutrition and Seafood Research, Denmark

Countries

Denmark

Continents

Europe

Description

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 PPARγ 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 PPARγ agonist suggesting a linkage between cell cycling and PPARγ ligand production. Indeed, cell cycle inhibitory compounds decreased PPARγ 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 PPARγ ligand production at the onset of adipocyte differentiation.

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NORA University Profiles

University of Southern Denmark

University of Copenhagen

Aarhus University

Dimensions Citation Indicators

Times Cited: 11

Field Citation Ratio (FCR): 1.37

Relative Citation ratio (RCR): 0.51

Open Access Info

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