Center for Healthcare Technology Development, Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
Biochem Biophys Res Commun. 2012 Apr 20;420(4):805-10. doi: 10.1016/j.bbrc.2012.03.078. Epub 2012 Mar 21.
18β-Glycyrrhetinic acid (18β-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18β-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18β-GA dose-dependently (1-40 μM) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 μM of 18β-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18β-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18β-GA alters fat mass by directly affecting adipogenesis in maturing preadipocytes and lipolysis in matured adipocytes. Thus, 18β-GA may be useful for the treatment of obesity.
18β-甘草次酸（18β-GA）来源于草药甘草，具有多种药理特性，包括抗炎和抗菌活性。然而，其潜在的生物抗肥胖活性尚不清楚。在这项研究中，鉴定了 18β-GA 在 3T3-L1 前体脂肪细胞的脂肪生成和分化脂肪细胞的脂肪分解中的新的生物学活性。使用胰岛素/地塞米松/3-异丁基-1-甲基黄嘌呤（IBMX）混合物诱导分化，将小鼠 3T3-L1 细胞用作体外脂肪生成和脂肪分解模型。通过 AdipoRed 测定法测定脂滴积累量。使用实时逆转录-聚合酶链反应（RT-PCR）和 Western blot 法研究几种脂肪生成转录因子和酶的表达。18β-GA 呈剂量依赖性（1-40 μM）显著减少成熟前体脂肪细胞中脂质的积累。在 3T3-L1 前体脂肪细胞中，10 μM 的 18β-GA 通过 Akt 磷酸化下调过氧化物酶体增殖物激活受体γ、CCAAT/增强子结合蛋白α和脂联素的转录水平，这些标志物是脂肪生成分化的标志。此外，在分化的脂肪细胞中，18β-GA 增加了甘油释放水平，并上调了激素敏感脂肪酶、脂肪甘油三酯脂肪酶和 perilipin 的 mRNA，以及激素敏感脂肪酶在丝氨酸 563 位点的磷酸化。结果表明，18β-GA 通过直接影响成熟前体脂肪细胞中的脂肪生成和成熟脂肪细胞中的脂肪分解来改变脂肪质量。因此，18β-GA 可能有助于肥胖的治疗。
