A prostaglandin J₂ metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation

Prostaglandins (PGs) of the J₂ 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 J₂ series of PGs remains unclear. Here, we report that PGJ₂ and its derivatives are efficacious activators of peroxisome proliferator-activated receptors α and γ (PPARγ and PPARγ, respectively), orphan nuclear receptors implicated in lipid homeostasis and adipocyte differentiation. The PGJ₂ metabolite 15-deoxy-Δ^12,14-PGJ₂ binds directly to PPARγ 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 PPARγ and, furthermore, suggest a novel mechanism of action for PGs of the J₂ series.