An adipogenic cofactor bound by the differentiation domain of PPARgamma

Open Access
Publisher Website
Google Scholar
Abstract
Ligand activation of the nuclear receptor PPARγ induces adipogenesis and increases insulin sensitivity, while activation of other PPAR isoforms (‐α and ‐δ) induces little or no fat cell differentiation. Expression and activation of chimeras formed between PPARγ and PPARδ in fibroblasts has allowed us to localize a major domain of PPARγ responsible for adipogenesis to the N‐terminal 138 amino acids, a region with AF‐1 transcriptional activity. Using this region of PPARγ as bait, we have used a yeast two‐hybrid screen to clone a novel protein, termed PGC‐2, containing a partial SCAN domain. PGC‐2 binds to and increases the transcriptional activity of PPARγ but does not interact with other PPARs or most other nuclear receptors. Ectopic expression of PGC‐2 in preadipocytes containing endogenous PPARγ causes a dramatic increase in fat cell differentiation at both the morphological and molecular levels. These results suggest that interactions between PGC‐2, a receptor isoform‐selective cofactor and PPARγ contribute to the adipogenic action of this receptor.

This publication has 45 references indexed in Scilit: