A PROSTAGLANDIN J(2) METABOLITE BINDS PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA AND PROMOTES ADIPOCYTE DIFFERENTIATION

Prostaglandins (PGs) of the J(2) series form in vivo and exert effects on a variety of biological processes. While most PGs mediate their effects through G protein-coupled receptors, the mechanism of action for the J(2) series of PGs remains unclear. Here, we report that PGJ(2) and its derivatives are efficacious activators of peroxisome proliferator-activated receptors alpha and gamma (PPAR alpha and PPAR gamma, respectively), orphan nuclear receptors implicated in lipid homeostasis and adipocyte differentiation. The PGJ(2) metabolite 15-deoxy-Delta(12,14)-PGJ(2) binds directly to PPAR gamma and promotes efficient differentiation of C3H10T1/2 fibroblasts to adipocytes. These data provide strong evidence that a fatty acid metabolite can function as an adipogenic agent through direct interactions with PPAR gamma and, furthermore, suggest a novel mechanism of action for PGs of the J(2) series.