Graduate school of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
Tohoku J Exp Med. 2009 Sep;219(1):53-62. doi: 10.1620/tjem.219.53.
Abnormal lipid metabolism in adipose tissue is closely related to the occurrence and progression of a wide variety of metabolic syndromes. We have analyzed the pharmacological effects of Chinese herbal medicines on cell differentiation and lipid metabolism in adipocytes. Yi-Gan-San (YGS) is a Chinese herbal medicine that is effective in treating the behavioral and psychological symptoms of dementia; however, its physiological mechanism remains unclear. We analyzed the effects of YGS on lipid accumulation in mouse 3T3-L1 adipocytes. Adipocyte differentiation was induced in mouse 3T3-L1 preadipocytes by treatment with the mixture of dexamethasone, 3-iso-butyl-1-methylxanthine, and insulin, and cells were cultured for 8 days with Chinese herbal medicines, including YGS. YGS effectively reduced the lipid accumulation in the differentiated 3T3-L1 cells in a dose-dependent manner, but had no effect on cell viability. YGS also reduced the activity of glycerol-3-phosphate dehydrogenase, an enzyme involved in lipid synthesis. In contrast, YGS gave no noticeable effect on glucose uptake and fatty acid uptake in the differentiated 3T3-L1 cells. Moreover, we established the stably transfected 3T3-L1 cell lines, each of which expresses the luciferase reporter gene under the control of sterol regulatory element-binding protein-1c (SREBP-1c) or FoxO1. SREBP-1c is a transcription factor involved in fatty acid synthesis, and FoxO1 is a forkhead-type transcription factor involved in adipocyte differentiation. Using these cell lines, we showed that YGS reduced the transcriptional activity of SREBP-1c, whereas YGS increased the activity of FoxO1. Thus, YGS may suppress lipid synthesis and fat accumulation in adipocytes through modulating the activities of SREBP-1c and FoxO1.
脂肪组织中脂质代谢的异常与多种代谢综合征的发生和发展密切相关。我们分析了中草药对脂肪细胞分化和脂质代谢的药理作用。一贯煎（YGS）是一种治疗痴呆行为和心理症状的有效中草药，但它的生理机制尚不清楚。我们分析了 YGS 对小鼠 3T3-L1 脂肪细胞脂质积累的影响。用地塞米松、3-异丁基-1-甲基黄嘌呤和胰岛素混合物诱导小鼠 3T3-L1 前脂肪细胞分化，并在含有 YGS 等中草药的条件下培养细胞 8 天。YGS 可有效剂量依赖性地减少分化的 3T3-L1 细胞中的脂质积累，但对细胞活力没有影响。YGS 还降低了参与脂质合成的甘油-3-磷酸脱氢酶的活性。相比之下，YGS 对分化的 3T3-L1 细胞中的葡萄糖摄取和脂肪酸摄取没有明显影响。此外，我们建立了稳定转染的 3T3-L1 细胞系，每个细胞系的荧光素酶报告基因均受固醇调节元件结合蛋白-1c（SREBP-1c）或 FoxO1 的控制。SREBP-1c 是一种参与脂肪酸合成的转录因子，FoxO1 是一种叉头型转录因子，参与脂肪细胞分化。使用这些细胞系，我们表明 YGS 降低了 SREBP-1c 的转录活性，而 YGS 增加了 FoxO1 的活性。因此，YGS 可能通过调节 SREBP-1c 和 FoxO1 的活性来抑制脂肪细胞中的脂质合成和脂肪积累。
