Tohoku J. Exp. Med., 2009, 219(1)

Chinese Herbal Medicine Yi-Gan-San Decreases the Lipid Accumulation in Mouse 3T3-L1 Adipocytes by Modulating the Activities of Transcription Factors SREBP-1c and FoxO1

MASAYUKI IZUMI,^1,2 TAKASHI SEKI,² KOH IWASAKI² and KAZUICHI SAKAMOTO¹

¹Graduate school of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan
²Center for Asian Traditional Medicine, Graduate School of Medicine, Tohoku University, Miyagi, Japan

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.

keywords —— Yi-Gan-San; SREBP-1c; FoxO; Adipocyte; 3T3-L1.

© 2009 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2009, 219, 53-62

Correspondence: Kazuichi Sakamoto, Graduate school of Life and Environmental Sciences, University of Tsukuba, Ibaraki, 305-8572 Japan.

e-mail: sakamoto@biol.tsukuba.ac.jp