Nartey Michael N N, Jisaka Mitsuo, Syeda Pinky Karim, Nishimura Kohji, Shimizu Hidehisa, Yokota Kazushige
The United Graduate School of Agricultural Sciences, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, Japan.
Council for Scientific and Industrial Research-Animal Research Institute, Achimota, Accra P.O. Box AH20, Ghana.
Life (Basel). 2023 Jan 29;13(2):370. doi: 10.3390/life13020370.
We previously reported that the addition of prostaglandin, (PG)D, and its chemically stable analog, 11-deoxy-11-methylene-PGD (11d-11m-PGD), during the maturation phase of 3T3-L1 cells promotes adipogenesis. In the present study, we aimed to elucidate the effects of the addition of PGD or 11d-11m-PGD to 3T3-L1 cells during the differentiation phase on adipogenesis. We found that both PGD and 11d-11m-PGD suppressed adipogenesis through the downregulation of peroxisome proliferator-activated receptor gamma (PPARγ) expression. However, the latter suppressed adipogenesis more potently than PGD, most likely because of its higher resistance to spontaneous transformation into PGJ derivatives. In addition, this anti-adipogenic effect was attenuated by the coexistence of an IP receptor agonist, suggesting that the effect depends on the intensity of the signaling from the IP receptor. The D-prostanoid receptors 1 (DP1) and 2 (DP2, also known as a chemoattractant receptor-homologous molecule expressed on Th2 cells) are receptors for PGD. The inhibitory effects of PGD and 11d-11m-PGD on adipogenesis were slightly attenuated by a DP2 agonist. Furthermore, the addition of PGD and 11d-11m-PGD during the differentiation phase reduced the DP1 and DP2 expression during the maturation phase. Overall, these results indicated that the addition of PGD or 11d-11m-PGD during the differentiation phase suppresses adipogenesis via the dysfunction of DP1 and DP2. Therefore, unidentified receptor(s) for both molecules may be involved in the suppression of adipogenesis.
我们之前报道过，在3T3-L1细胞的成熟阶段添加前列腺素（PG）D及其化学稳定类似物11-脱氧-11-亚甲基-PGD（11d-11m-PGD）可促进脂肪生成。在本研究中，我们旨在阐明在分化阶段向3T3-L1细胞中添加PGD或11d-11m-PGD对脂肪生成的影响。我们发现，PGD和11d-11m-PGD均通过下调过氧化物酶体增殖物激活受体γ（PPARγ）的表达来抑制脂肪生成。然而，后者比PGD更有效地抑制脂肪生成，这很可能是因为它对自发转化为PGJ衍生物具有更高的抗性。此外，IP受体激动剂的共存减弱了这种抗脂肪生成作用，这表明该作用取决于来自IP受体的信号强度。D-前列腺素受体1（DP1）和2（DP2，也称为Th2细胞上表达的趋化因子受体同源分子）是PGD的受体。DP2激动剂可使PGD和11d-11m-PGD对脂肪生成的抑制作用略有减弱。此外，在分化阶段添加PGD和11d-11m-PGD可降低成熟阶段DP1和DP2的表达。总体而言，这些结果表明，在分化阶段添加PGD或11d-11m-PGD可通过DP1和DP2功能障碍抑制脂肪生成。因此，这两种分子的未知受体可能参与了对脂肪生成的抑制。
