Lim Seona, Park Jinbong, Um Jae-Young
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea.
Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
Front Pharmacol. 2019 Oct 15;10:1154. doi: 10.3389/fphar.2019.01154. eCollection 2019.
Obesity is constantly rising into a major health threat worldwide. Activation of brown-like transdifferentiation of white adipocytes (browning) has been proposed as a promising molecular target for obesity treatment. In this study, we investigated the effect of ginsenoside Rb1 (Rb1), a saponin derived from Meyer, on browning. We used 3T3-L1 murine adipocytes and leptin receptor mutated db/db mice. The lipid accumulation, AMP-activated protein kinase alpha (AMPKα)-related pathways, lipolytic and thermogenic factors were measured after Rb treatment in 3T3-L1 adipocytes. Body weight change and lipolysis-thermogenesis factors were investigated in Rb1-treated db/db mice. Beta 3 adrenergic receptor activation (β3AR) changes were measured in Rb1-treated 3T3-L1 cells with or without β3AR inhibitor L748337 co-treatment. As a result, Rb1 treatment decreased lipid droplet size in 3T3-L1 adipocytes. Rb1 also induced phosphorylations of AMPKα pathway and sirtuins. Moreover, lipases and thermogenic factors such as uncoupling protein 1 were increased by Rb1 treatment. Through these results, we could expect that the non-shivering thermogenesis program can be induced by Rb1. In db/db mice, 6-week injection of Rb1 resulted in decreased inguinal white adipose tissue (iWAT) weight associated with shrunken lipid droplets and increased lipolysis and thermogenesis. The thermogenic effect of Rb1 was possibly due to β3AR, as L748337 pre-treatment abolished the effect of Rb1. In conclusion, we suggest Rb1 as a potential lipolytic and thermogenic therapeutic agent which can be used for obesity treatment.
肥胖正持续成为全球范围内的一个主要健康威胁。白色脂肪细胞向棕色样细胞的转分化（褐变）激活已被提议作为肥胖治疗的一个有前景的分子靶点。在本研究中，我们调查了源自人参的皂苷人参皂苷Rb1（Rb1）对褐变的影响。我们使用了3T3-L1小鼠脂肪细胞和瘦素受体突变的db/db小鼠。在Rb处理3T3-L1脂肪细胞后，测量脂质积累、AMP激活的蛋白激酶α（AMPKα）相关途径、脂解和产热因子。在经Rb1处理的db/db小鼠中研究体重变化和脂解-产热因子。在有或没有β3肾上腺素能受体抑制剂L748337共同处理的情况下，测量经Rb1处理的3T3-L1细胞中的β3肾上腺素能受体激活（β3AR）变化。结果，Rb1处理减小了3T3-L1脂肪细胞中的脂滴大小。Rb1还诱导了AMPKα途径和去乙酰化酶的磷酸化。此外，Rb1处理增加了脂肪酶和产热因子，如解偶联蛋白1。通过这些结果，我们可以预期Rb1可诱导非寒战产热程序。在db/db小鼠中，6周注射Rb1导致腹股沟白色脂肪组织（iWAT）重量减轻，伴有脂滴缩小以及脂解和产热增加。Rb1的产热作用可能归因于β3AR，因为L748337预处理消除了Rb1的作用。总之，我们建议将Rb1作为一种潜在的脂解和产热治疗剂，可用于肥胖治疗。
