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: Masayuki Izumi, Takashi Seki, Koh Iwasaki, Kazuichi Sakamoto
• Journal: The Tohoku journal of experimental medicine (Tohoku J Exp Med) Vol. 219 Issue 1 Pg. 53-62 (Sep 2009) ISSN: 1349-3329 [Electronic] Japan
• PMID: 19713685 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• Fatty Acids
• Forkhead Box Protein O1
• Forkhead Transcription Factors
• Foxo1 protein, mouse
• Srebf1 protein, mouse
• Sterol Regulatory Element Binding Protein 1
• Yi-Gan San
• bu-zhong-yi-qi-tang
• liu-jun-zi-tang
• Glycerolphosphate Dehydrogenase
• Glucose

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, drug effects, metabolism)
• Animals
• Cell Survival (drug effects)
• Drugs, Chinese Herbal (pharmacology)
• Fatty Acids (metabolism)
• Forkhead Box Protein O1
• Forkhead Transcription Factors (genetics, metabolism)
• Gene Expression (drug effects, genetics)
• Glucose (metabolism)
• Glycerolphosphate Dehydrogenase (metabolism)
• Lipid Metabolism (drug effects)
• Mice
• Reverse Transcriptase Polymerase Chain Reaction
• Sterol Regulatory Element Binding Protein 1 (genetics, metabolism)