Cell
Volume 83, Issue 5, 1 December 1995, Pages 803-812
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Article
15-Deoxy-Δ12,14-Prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ

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Abstract

Regulation of adipose cell mass is a critical homeostatic process in higher vertebrates. The conversion of fibroblasts into cells of the adipose lineage is induced by expression of the orphan nuclear receptor PPARyγ. This suggests that an endogenous PPARγ ligand may be an important regulator of adipogenesis. By assaying arachidonate metabolites for their capacity to activate PPAR response elements, we have identified 15-deoxy-Δ12,14-prostaglandin J2 as both a PPARγ ligand and an inducer of adipogenesis. Similarly, the thiazolidinedione class of antidiabetic drugs also bind to PPARγ and act as potent regulators of adipocyte development. Thus, adipogenic prostanoids and antidiabetic thiazolidinediones initiate key transcriptional events through a common nuclear receptor signaling pathway. These findings suggest a pivotal role for PPARγ and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders.

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