Prostaglandins(PGs) of the Jz 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 JL series of PGs remains unclear. Here, we report that PGJ? and its derivatives are efficacious activators of peroxisome proliferator-activated receptors a and y (PPARa and PPART, respectively), orphan nuclear receptors implicated in lipid homeostasis and adipocyte differentiation. The PGJ2 metabolite lgdeoxy-A12, t4-PGJ2 binds directly to PPARy and promotes efficient differentiation of C3HlOT1/2 fibroblasts to adipocytes. These data provide strong evidence that a fatty acid metabolite can function as an adipogenic agent through direct interactions with PPARy and, furthermore, suggest a novel mechanism of action for PGs of the J2 series.