15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) IS A LIGAND FOR THE ADIPOCYTE DETERMINATION FACTOR PPAR-GAMMA

Regulation of adipose cell mass is a critical homeostatic process in h igher vertebrates. The conversion of fibroblasts into cells of the adi pose lineage is induced by expression of the orphan nuclear receptor P PAR gamma. This suggests that an endogenous PPAR gamma ligand mar be a n important regulator of adipogenesis. By assaying arachidonate metabo lites for their capacity to activate PPAR response elements, we have i dentified 15-deoxy-Delta(12,14)-prostaglandin J(2) as both a PPAR gamm a ligand and an inducer of adipogenesis. Similarly, the thiazolidinedi one class of antidiabetic drugs also bind to PPAR gamma and act as pot ent regulators of adipocyte development. Thus, adipogenic prostanoids and antidiabetic thiazolidinediones initiate key transcriptional event s through a common nuclear receptor signaling pathway. These findings suggest a pivotal role for PPAR gamma and its endogenous ligand in adi pocyte development and glucose homeostasis and as a target for interve ntion in metabolic disorders.