Wakai Eri, Aritake Kosuke, Urade Yoshihiro, Fujimori Ko
Laboratory of Pathobiochemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Laboratory of Chemical Pharmacology, Daiichi University of Pharmacy, 22-1 Tamagawa-cho, Minami-Ku, Fukuoka 815-8511, Japan.
Biochem Biophys Res Commun. 2017 Aug 19;490(2):393-399. doi: 10.1016/j.bbrc.2017.06.053. Epub 2017 Jun 13.
Prostaglandin (PG) D enhanced lipid accumulation in adipocytes. However, its molecular mechanism remains unclear. In this study, we investigated the regulatory mechanisms of PGD-elevated lipid accumulation in mouse adipocytic 3T3-L1 cells. The Gi-coupled DP2 (CRTH2) receptors (DP2R), one of the two-types of PGD receptors were dominantly expressed in adipocytes. A DP2R antagonist, CAY10595, but not DP1 receptor antagonist, BWA868C cleared the PGD-elevated intracellular triglyceride level. While, a DP2R agonist, 15R-15-methyl PGD (15R) increased the mRNA levels of the adipogenic and lipogenic genes, and decreased the glycerol release level. In addition, the forskolin-mediated increase of cAMP-dependent protein kinase A (PKA) activity and phosphorylation of hormone-sensitive lipase (HSL) was repressed by the co-treatment with 15R. Moreover, the lipolysis was enhanced in the adipocyte-differentiated DP2R gene-knockout mouse embryonic fibroblasts. These results indicate that PGD suppressed the lipolysis by repression of the cAMP-PKA-HSL axis through DP2R in adipocytes.
前列腺素（PG）D可增强脂肪细胞中的脂质积累。然而，其分子机制仍不清楚。在本研究中，我们调查了PGD升高小鼠脂肪细胞3T3-L1中脂质积累的调控机制。两种类型的PGD受体之一，与Gi偶联的DP2（CRTH2）受体（DP2R）在脂肪细胞中占主导地位表达。一种DP2R拮抗剂CAY10595可清除PGD升高的细胞内甘油三酯水平，而DP1受体拮抗剂BWA868C则不能。同时，一种DP2R激动剂15R-15-甲基PGD（15R）可增加脂肪生成和脂质生成基因的mRNA水平，并降低甘油释放水平。此外，15R与福斯高林共同处理可抑制其介导的cAMP依赖性蛋白激酶A（PKA）活性增加以及激素敏感性脂肪酶（HSL）的磷酸化。此外，在脂肪细胞分化的DP2R基因敲除小鼠胚胎成纤维细胞中脂解作用增强。这些结果表明，PGD通过在脂肪细胞中通过DP2R抑制cAMP-PKA-HSL轴来抑制脂解作用。
