A human peroxisome-proliferator-activated receptor-γ is activated by inducers of adipogenesis, including thiazalidinedione drugs

Abstract

We have cloned a human cognate of the mouse peroxisome-proliferator-activated receptor-γ (hPPARγ) from a human placenta cDNA library. Sequence analysis reveals a high degree of similarity with the mouse receptor and, like other PPAR, hPPARγ forms heterodimers with the retinoid X receptor α (RXRα) and binds in vitro to DNA elements containing direct repeats of the sequence TGACCT. In common with mouse PPARγ, hPPARγ is expressed strongly in adipose tissue, but significant levels also are detectable in placenta, lung and ovary. In vitro trans-activation data suggest hPPARγ is only poorly activated by xenobiotic peroxisome proliferators, although certain fatty acids and eicosanoids are potent activators of this receptor. Both mouse and human PPARγ, are capable of being activated by thiazolidinedione drugs, although the two receptors appear to differ in their sensitivity to these compounds. Taken together, these data suggest a high degree of structural and functional similarity between mouse and human PPARγ, and provide evidence for variation in human receptor structure which may result in differential sensitivity to activators.