PPARβ/δ potentiates PPARγ‐stimulated adipocyte differentiation

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Abstract
It is well established that peroxisome proliferator-activated receptor-gamma (PPARgamma) has a critical role in modulating adipocyte differentiation based on gain-of-function and loss-of-function experiments. However, recent gain-of-function experiments suggest that PPARbeta may also have a role in mediating adipocyte differentiation. Because ligands for PPARs can activate more than one receptor isoform, the specific role of PPARbeta in adipocyte differentiation was examined using PPARbeta-null adipocytes. Wild-type adipocytes accumulate lipids in response to differentiation signaling induced from standard differentiation medium, and this effect is significantly reduced in PPARbeta-null adipocytes. The addition of the PPARbeta ligand L165041 to the standard differentiation medium causes enhanced adipocyte differentiation and lipid accumulation, and this effect is diminished in adipocytes lacking expression of PPARbeta. Treatment of wild-type adipocytes with the PPARgamma ligand troglitazone causes accelerated adipocyte differentiation and lipid accumulation, and this effect is marginally reduced in PPARbeta-null adipocytes. Expression patterns of mRNA markers of early and late adipocyte differentiation are consistent with the morphological and biochemical differences observed. Results from these studies demonstrate that in the absence of PPARbeta expression, adipocyte differentiation is significantly impaired, providing loss-of-function evidence supporting a role for this receptor in adipocyte differentiation. These results also demonstrate that L165041-stimulated adipocyte differentiation and lipid accumulation is mediated by PPARbeta. In addition, as the ability of troglitazone to induce adipocyte differentiation is also impaired in PPARbeta null adipocytes, this suggests that both PPARbeta and PPARgamma isoforms are required to facilitate maximal lipid accumulation and differentiation during adipogenesis.
Funding Information
  • National Institutes of Health (RO1 CA89607, CA97999)

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