Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Department of Pathobiochemistry, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Chem Biol Interact. 2021 Sep 1;346:109595. doi: 10.1016/j.cbi.2021.109595. Epub 2021 Jul 21.
Glycyrrhizic acid (GA), a major constituent of the root of licorice (Glycyrrhiza glabra), and has various biological activities, including anti-obesity property. However, the molecular mechanism of anti-adipogenic effect of GA is still unclear. In this study, we investigated the anti-adipogenic effects of GA in mouse adipocytic 3T3-L1 cells and elucidated its underlying molecular mechanism. GA decreased the intracellular triglyceride level. The expression levels of the adipogenic and lipogenic genes were lowered by treatment with GA in a concertation-dependent manner. In contrast, GA did not affect the lipolytic gene expression and the released glycerol level. GA suppressed the early stage of adipogenesis when it was added for 0-3 h after initiation of adipogenesis. Moreover, GA reduced the mRNA levels of CCAAT/enhancer binding protein (C/EBP) β and C/EBPδ, both of which activate the early stage of adipogenesis. Furthermore, GA decreased phosphorylation of extracellular signal-regulated kinase [ERK: p44/42 mitogen-activated protein kinase (MAPK)] in the early stage of adipogenesis. In addition, a MAPK kinase (MEK) inhibitor, PD98059 reduced the C/EBPβ and C/EBPδ gene expression. These results indicate that GA suppressed the early stage of adipogenesis through repressing the MEK/ERK-mediated C/EBPβ and C/EBPδ expression in 3T3-L1 cells. Thus, GA has an anti-adipogenic ability and a possible agent for treatment of obesity.
甘草酸（GA）是甘草（Glycyrrhiza glabra）根的主要成分，具有多种生物活性，包括抗肥胖作用。然而，GA 抗脂肪生成作用的分子机制尚不清楚。在本研究中，我们研究了 GA 在小鼠脂肪细胞 3T3-L1 细胞中的抗脂肪生成作用，并阐明了其潜在的分子机制。GA 降低了细胞内甘油三酯水平。GA 以浓度依赖的方式降低了脂肪生成和脂生成基因的表达水平。相比之下，GA 不影响脂肪分解基因的表达和释放的甘油水平。GA 在脂肪生成开始后 0-3 小时添加时抑制了脂肪生成的早期阶段。此外，GA 降低了 CCAAT/增强子结合蛋白（C/EBP）β和 C/EBPδ的 mRNA 水平，这两者都激活了脂肪生成的早期阶段。此外，GA 降低了脂肪生成早期阶段细胞外信号调节激酶 [ERK：p44/42 丝裂原激活蛋白激酶（MAPK）]的磷酸化。此外，MAPK 激酶（MEK）抑制剂 PD98059 降低了 C/EBPβ 和 C/EBPδ 基因的表达。这些结果表明，GA 通过抑制 MEK/ERK 介导的 3T3-L1 细胞中 C/EBPβ 和 C/EBPδ 的表达来抑制脂肪生成的早期阶段。因此，GA 具有抗脂肪生成能力，可能是治疗肥胖的一种药物。
