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Gene. 2012 Aug 15;505(1):46-52. doi: 10.1016/j.gene.2012.05.052. Epub 2012 Jun 1.

Activation of adipogenesis by lipocalin-type prostaglandin D synthase-generated Δ¹²-PGJ₂ acting through PPARγ-dependent and independent pathways.

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Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.


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 Δ(12)-PGJ(2), one of the PGD(2) metabolites, was predominantly produced in the differentiated 3T3-L1 cells. Δ(12)-PGJ(2) enhanced the expression of adipogenic genes in a Δ(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 Δ(12)-PGJ(2). Moreover, the production of adiponectin and leptin was increased by treatment with Δ(12)-PGJ(2). Furthermore, the results of a mammalian two-hybrid assay demonstrated that Δ(12)-PGJ(2) enhanced the PPARγ-mediated transcription activity. However, Δ(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 PPARγ 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 PPARγ-independent mechanism for Δ(12)-PGJ(2)-activated adipogenesis. These results, taken together, indicate that Δ(12)-PGJ(2) is a dominant metabolite of L-PGDS-produced PGD(2) during adipogenesis and acts as an activator for adipogenesis through both PPARγ-dependent and -independent mechanisms in 3T3-L1 cells.

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