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

Fujimori, Ko; Maruyama, Toshisuke; Kamauchi, Shinya; Urade, Yoshihiro

doi:10.1016/j.gene.2012.05.052

Cited by 28 publications

(18 citation statements)

References 33 publications

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“…PGD 2 is nonenzymatically metabolized to PGs of the J series, that is, PGJ 2 , Δ 12 -PGJ 2 , and 15d-PGJ 2 . However, the concentrations of 15d-PGJ 2 required for the activation of PPAR γ reported in most of the literature are much higher (2.5–100 μ mol/L) than those of conventional PGs (pmol/L range); and 15d-PGJ 2 is present in vivo at a low level that is insufficient for activation of adipocyte differentiation [65], whose finding is consistent with our current results indicating that 15d-PGJ 2 is not detectable in adipocytes [60]. Recently, we identified Δ 12 -PGJ 2 as being the dominant PGD 2 metabolite in differentiated adipocytes [60], in good agreement with recent results showing that Δ 12 -PGJ 2 is produced in adipocytes and activates the expression of adipogenic genes in 3T3-L1 cells [66].…”

Section: Acceleration Of Adipocyte Differentiation By Pgd2 and Itssupporting

confidence: 91%

“…Finally, we found that mPGES-1 is responsible for the production of PGE 2 in adipocytes [60]. This result is consistent with results showing that treatment of mouse embryonic fibroblast (MEF) cells with PGE 2 for the first two days of adipocyte differentiation is enough to suppress adipocyte differentiation, with reduced expression of the PPAR γ 2 gene and reduced accumulation of intracellular lipids [43].…”

Section: Suppression Of the Early Phase Of Adipogenesis By Pge2supporting

confidence: 85%

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Prostaglandins as PPARγModulators in Adipogenesis

Fujimori

2012

PPAR Research

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Adipocytes and fat cells play critical roles in the regulation of energy homeostasis. Adipogenesis (adipocyte differentiation) is regulated via a complex process including coordinated changes in hormone sensitivity and gene expression. PPARγ is a ligand-dependent transcription factor and important in adipogenesis, as it enhances the expression of numerous adipogenic and lipogenic genes in adipocytes. Prostaglandins (PGs), which are lipid mediators, are associated with the regulation of PPARγ function in adipocytes. Prostacyclin promotes the differentiation of adipocyte-precursor cells to adipose cells via activation of the expression of C/EBPβ and δ. These proteins are important transcription factors in the activation of the early phase of adipogenesis, and they activate the expression of PPARγ, which event precedes the maturation of adipocytes. PGE2 and PGF2α strongly suppress the early phase of adipocyte differentiation by enhancing their own production via receptor-mediated elevation of the expression of cycloxygenase-2, and they also suppress the function of PPARγ. In contrast, PGD2 and its non-enzymatic metabolite, Δ12-PGJ2, activate the middle-late phase of adipocyte differentiation through both DP2 receptors and PPARγ. This paper focuses on potential roles of PGs as PPARγ modulators in adipogenesis and regulators of obesity.

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Section: Acceleration Of Adipocyte Differentiation By Pgd2 and Itssupporting

confidence: 91%

Section: Suppression Of the Early Phase Of Adipogenesis By Pge2supporting

confidence: 85%

Prostaglandins as PPARγModulators in Adipogenesis

Fujimori

2012

PPAR Research

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“…Apoptotic cells stimulate the production of the identified PPAR ligands, such as 15lipoxygenase-dependent 15-hydroxyeicosatetraenoic acid (HETE), lipoxin A4, and PGD2 synthase-dependent 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) (Fujimori et al, 2012, Korns et al, 2011. Consistent with these findings, we observed enhanced production of these PPAR ligands in ApoSQ-exposed CM ( Figure 4A-C).…”

Section: Secreted Ppar Ligands From Macrophages Mediate Anti-emt Effsupporting

confidence: 83%

Programming of macrophages by apoptotic cancer cells inhibits cancer progression through exosomal PTEN and PPARγ ligands

Kim¹,

Ahn²,

J³

et al. 2017

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“…PGD 2 [11] and its metabolite, Δ 12 -PGJ 2 [12], activate the middle-late phase of adipogenesis, and PGD 2 -overproducing mice become obese under the high-fat diet [13]. Moreover, prostacyclin (PGI 2 ) enhances adipogenesis through PGI 2 receptor [14], [15].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Suppression of Early Phase of Adipogenesis by Microsomal PGE Synthase-1 (PTGES1)-Produced PGE2 and Aldo-Keto Reductase 1B3-Produced PGF2α

2012

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We recently reported that aldo-keto reductase 1B3-produced prostaglandin (PG) F2α suppressed the early phase of adipogenesis. PGE2 is also known to suppress adipogenesis. In this study, we found that microsomal PGE2 synthase (PGES)-1 (mPGES-1; PTGES1) acted as the PGES in adipocytes and that PGE2 and PGF2α synergistically suppressed the early phase of adipogenesis. PGE2 production was detected in preadipocytes and transiently enhanced at 3 h after the initiation of adipogenesis of mouse adipocytic 3T3-L1 cells, followed by a quick decrease; and its production profile was similar to the expression of the cyclooxygenase-2 (PTGS2) gene. When 3T3-L1 cells were transfected with siRNAs for any one of the three major PTGESs, i.e., PTGES1, PTGES2 (mPGES-2), and PTGES3 (cytosolic PGES), only PTGES1 siRNA suppressed PGE2 production and enhanced the expression of adipogenic genes. AE1-329, a PTGER4 (EP4) receptor agonist, increased the expression of the Ptgs2 gene with a peak at 1 h after the initiation of adipogenesis. PGE2-mediated enhancement of the PTGS2 expression was suppressed by the co-treatment with L-161982, a PTGER4 receptor antagonist. Moreover, AE1-329 enhanced the expression of the Ptgs2 gene by binding of the cyclic AMP response element (CRE)-binding protein to the CRE of the Ptgs2 promoter; and its binding was suppressed by co-treatment with L-161982, which was demonstrated by promoter luciferase and chromatin immunoprecipitation assays. Furthermore, when 3T3-L1 cells were caused to differentiate into adipocytes in medium containing both PGE2 and PGF2α, the expression of the adipogenic genes and the intracellular triglyceride level were decreased to a greater extent than in medium containing either of them, revealing that PGE2 and PGF2α independently suppressed adipogenesis. These results indicate that PGE2 was synthesized by PTGES1 in adipocytes and synergistically suppressed the early phase of adipogenesis of 3T3-L1 cells in cooperation with PGF2α through receptor-mediated activation of PTGS2 expression.

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

Cited by 28 publications

References 33 publications

Prostaglandins as PPARγModulators in Adipogenesis

Prostaglandins as PPARγModulators in Adipogenesis

Programming of macrophages by apoptotic cancer cells inhibits cancer progression through exosomal PTEN and PPARγ ligands

Synergistic Suppression of Early Phase of Adipogenesis by Microsomal PGE Synthase-1 (PTGES1)-Produced PGE2 and Aldo-Keto Reductase 1B3-Produced PGF2α

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