Journal
GENE
Volume 505, Issue 1, Pages 46-52Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2012.05.052
Keywords
Adipocytes; Delta(12)-PGJ(2); L-PGDS; PPAR gamma; Adipocytokines; 3T3-L1
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21570151, 23116516]
- Japan Foundation for Applied Enzymology
- Research Foundation for Pharmaceutical Sciences
- Naito Foundation
- Takeda Science Foundation
- Osaka City
- Grants-in-Aid for Scientific Research [21570151] Funding Source: KAKEN
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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. (C) 2012 Elsevier B.V. All rights reserved.
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