Comparison of pro-adipogenic effects between prostaglandin (PG) D2 and its stable, isosteric analogue, 11-deoxy-11-methylene-PGD2, during the maturation phase of cultured adipocytes

Prostaglandin D2 Added during the Differentiation of 3T3-L1 Cells Suppresses Adipogenesis via Dysfunction of D-Prostanoid Receptor P1 and P2

“…We evaluated the adipogenic differentiation of the 3T3-L1 cells based on the MDI-induced intracellular TAG accumulation. In contrast to our previous findings regarding the pro-adipogenic effects of the addition of PGD 2 or 11d-11m-PGD 2 to cells during the maturation phase [ 36 ], both PGs attenuated the MDI-induced intracellular TAG accumulation ( Figure 1 B). Furthermore, 11d-11m-PGD 2 was more anti-adipogenic than PGD 2 ( Figure 1 B).…”

“…We initially examined how the 3T3-L1 cells responded to the addition of PGD 2 or 11d-11m-PGD 2 during the differentiation phase, which were pro-adipogenic when added during the maturation phase [ 36 ] ( Figure 1 A). We evaluated the adipogenic differentiation of the 3T3-L1 cells based on the MDI-induced intracellular TAG accumulation.…”

“…We analyzed the inhibitory effects of PGD 2 and 11d-11m-PGD 2 on MDI-induced adipogenesis using selective agonists for PGD 2 receptors, DP1 and DP2, during the differentiation phase, because the activation of these receptors promotes adipogenesis during the maturation phase [ 35 , 36 ] ( Figure 4 A). The selective DP1 agonist, BW245C, and the selective DP2 agonist, 15 R -15m-PGD 2 , were used at the previously reported concentrations [ 35 , 36 ]. The selective DP1 agonist, BW245C, did not affect the anti-adipogenic effects of PGD 2 or 11d-11m-PGD 2 ( Figure 4 B).…”

“…The incubation of the 3T3-L1 cells with PGD 2 or 11d-11m-PGD 2 for two days in the differentiation phase significantly reduced the DP1 and DP2 expression on day six in the maturation phase ( Figure 5 B,C). As DP1 and DP2 contribute to the promotion of adipogenesis during the maturation phase [ 36 ], these results suggest that the addition of PGD 2 and 11d-11m-PGD 2 during the differentiation phase exerts anti-adipogenic effects by decreasing the DP1 and DP2 expression during the maturation phase.…”

“…PGD 2 is biosynthesized via lipocalin-type PGD synthase (L-PGDS), which is preferentially expressed in adipocytes from PGH 2 produced from arachidonic acid via COXs [ 21 ] and is also known as a precursor to PGJ 2 derivatives [ 34 ]. In addition to the increased transcriptional activity of PPARγ induced by PGD 2 [ 27 , 28 ], the addition of PGD 2 during the maturation phase promotes MDI-induced adipogenesis by binding and activating D-prostanoid 1 (DP1) and/or 2 receptor (DP2, also known as a chemoattractant receptor-homologous molecule expressed on TH 2 cells) [ 35 , 36 ]. Based on these reports, PGD 2 is considered to be pro-adipogenic.…”