15-deoxy-Δ12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ

BM Forman, P Tontonoz, J Chen, RP Brun… - Cell, 1995 - cell.com
BM Forman, P Tontonoz, J Chen, RP Brun, BM Spiegelman, RM Evans
Cell, 1995cell.com
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 PPART. This suggests that an endogenous PPARy 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-A12~ 14-
prostaglandin J2 as both a PPARy ligand and an inducer of adipogenesis. Similarly, the …
Summary
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 PPART. This suggests that an endogenous PPARy 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-A12~ 14-prostaglandin J2 as both a PPARy ligand and an inducer of adipogenesis. Similarly, the thiazolidinedione class of antidiabetic drugs also bind to PPARy 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 PPART and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders.
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