Activation of adipogenesis by lipocalin-type prostaglandin D synthase-generated Delta(12)-PGJ(2) acting through PPAR gamma-dependent and independent pathways

作者：Fujimori Ko^*; Maruyama Toshihiko; Kamauchi Shinya; Urade Yoshihiro

来源：Gene, 2012, 505(1): 46-52.

DOI：10.1016/j.gene.2012.05.052

• Adipocytes
• Delta(12)-PGJ(2)
• L-PGDS
• PPAR gamma
• Adipocytokines
• 3T3-L1

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS)-produced PGD(2) accelerates adipogenesis. In this study, we investigated the molecular mechanism of PGD(2)-mediated activation of adipogenesis in mouse adipocytic 3T3-L1 cells. LC/MS analysis showed that Delta(12)-PGJ(2), one of the PGD(2) metabolites, was predominantly produced in the differentiated 3T3-L1 cells. Delta(12)-PGJ(2) enhanced the expression of adipogenic genes in a Delta(12)-PGJ(2)-concentration-dependent manner. Suppression of the expression of the adipogenic genes by L-PGDS siRNA or AT-56, an L-PGDS inhibitor, was cleared by the addition of Delta(12)-PGJ(2). Moreover, the production of adiponectin and leptin was increased by treatment with Delta(12)-PGJ(2). Furthermore, the results of a mammalian two-hybrid assay demonstrated that Delta(12)-PGJ(2) enhanced the PPAR gamma-mediated transcription activity. However, Delta(12)-PGJ(2)-activated expression of adipogenic genes such as fatty acid binding protein 4 (aP2) and stearoyl-CoA desaturase was inhibited only at 38% and 42%, respectively, by treatment with GW9662, a PPAR gamma antagonist in 3T3-L1 cells, although Troglitazone-mediated activation of the expression of these adipogenic genes was completely suppressed by GW9662, suggesting the existence of a PPAR gamma-independent mechanism for Delta(12)-PGJ(2)-activated adipogenesis. These results, taken together, indicate that Delta(12)-PGJ(2) is a dominant metabolite of L-PGDS-produced PGD(2) during adipogenesis and acts as an activator for adipogenesis through both PPAR gamma-dependent and -independent mechanisms in 3T3-L1 cells.

• 出版日期2012-8-15