کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2817625 | 1160001 | 2012 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Activation of adipogenesis by lipocalin-type prostaglandin D synthase-generated Δ12-PGJ2 acting through PPARγ-dependent and independent pathways Activation of adipogenesis by lipocalin-type prostaglandin D synthase-generated Δ12-PGJ2 acting through PPARγ-dependent and independent pathways](/preview/png/2817625.png)
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS)-produced PGD2 accelerates adipogenesis. In this study, we investigated the molecular mechanism of PGD2-mediated activation of adipogenesis in mouse adipocytic 3T3-L1 cells. LC/MS analysis showed that Δ12-PGJ2, one of the PGD2 metabolites, was predominantly produced in the differentiated 3T3-L1 cells. Δ12-PGJ2 enhanced the expression of adipogenic genes in a Δ12-PGJ2-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 Δ12-PGJ2. Moreover, the production of adiponectin and leptin was increased by treatment with Δ12-PGJ2. Furthermore, the results of a mammalian two-hybrid assay demonstrated that Δ12-PGJ2 enhanced the PPARγ-mediated transcription activity. However, Δ12-PGJ2-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 Δ12-PGJ2-activated adipogenesis. These results, taken together, indicate that Δ12-PGJ2 is a dominant metabolite of L-PGDS-produced PGD2 during adipogenesis and acts as an activator for adipogenesis through both PPARγ-dependent and -independent mechanisms in 3T3-L1 cells.
► Δ12-PGJ2 is a major metabolite L-PGDS-produced PGD2 in adipocytes.
► Δ12-PGJ2 binds and activates PPARγ function.
► Δ12-PGJ2 activates adipogenesis through PPARγ-dependent and -independent mechanisms.
Journal: Gene - Volume 505, Issue 1, 15 August 2012, Pages 46–52