Prostaglandin D(2) Added during the Differentiation of 3T3-L1 Cells Suppresses Adipogenesis via Dysfunction of D-Prostanoid Receptor P1 and P2

We previously reported that the addition of prostaglandin, (PG)D(2), and its chemically stable analog, 11-deoxy-11-methylene-PGD(2) (11d-11m-PGD(2)), during the maturation phase of 3T3-L1 cells promotes adipogenesis. In the present study, we aimed to elucidate the effects of the addition of PGD(2) or 11d-11m-PGD(2) to 3T3-L1 cells during the differentiation phase on adipogenesis. We found that both PGD(2) and 11d-11m-PGD(2) suppressed adipogenesis through the downregulation of peroxisome proliferator-activated receptor gamma (PPARγ) expression. However, the latter suppressed adipogenesis more potently than PGD(2), most likely because of its higher resistance to spontaneous transformation into PGJ(2) derivatives. In addition, this anti-adipogenic effect was attenuated by the coexistence of an IP receptor agonist, suggesting that the effect depends on the intensity of the signaling from the IP receptor. The D-prostanoid receptors 1 (DP1) and 2 (DP2, also known as a chemoattractant receptor-homologous molecule expressed on Th2 cells) are receptors for PGD(2). The inhibitory effects of PGD(2) and 11d-11m-PGD(2) on adipogenesis were slightly attenuated by a DP2 agonist. Furthermore, the addition of PGD(2) and 11d-11m-PGD(2) during the differentiation phase reduced the DP1 and DP2 expression during the maturation phase. Overall, these results indicated that the addition of PGD(2) or 11d-11m-PGD(2) during the differentiation phase suppresses adipogenesis via the dysfunction of DP1 and DP2. Therefore, unidentified receptor(s) for both molecules may be involved in the suppression of adipogenesis.