title: 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.
abstract: 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.
authors.affiliation: Graduate school of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Izumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Seki
authors.forename: Koh
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Sakamoto
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D005227:Fatty Acids; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; C524644:Yi-Gan San; C402943:bu-zhong-yi-qi-tang; C084136:liu-jun-zi-tang; D005993:Glycerolphosphate Dehydrogenase; D005947:Glucose