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Rubrofusarin-6-β-gentiobioside inhibits lipid accumulation and weight gain by regulating AMPK/mTOR signaling

Han, Yo-Han, Kee, Ji-Ye, Park, Seong-Hwan, Mun, Jeong-Geon, Jeon, Hee-Dong, Park, Jinbong, Zou, Qin-Peng, Liu, Xiang-Qian, Hong, Seung-Heon
Phytomedicine 2019 v.62 pp. 152952
AMP-activated protein kinase, Western blotting, animal disease models, binding proteins, blood serum, eosin, epididymis, fatty liver, fluorescent antibody technique, high fat diet, humans, hyperlipidemia, in vitro studies, lipids, liver, mesenchymal stromal cells, mice, obesity, peroxisome proliferator-activated receptors, quantitative polymerase chain reaction, rapamycin, reverse transcriptase polymerase chain reaction, staining, therapeutics, weight gain, white adipose tissue
Although rubrofusarin-6-β-gentiobioside (RFG), which is a component of Cassiae tora seed, could likely regulate hyperlipidemia, its anti-obesity effect and related mechanism have not been elucidated.The aim of this study was to examine whether RFG can ameliorate obesity and the mechanism of lipid accumulation regulated by RFG.In in vitro experiments, we confirmed the anti-adipogenic effect of RFG using 3T3-L1 cells and human adipose mesenchymal stem cells (hAMSCs). To confirm the anti-obesity effect, High-Fat Diet (HFD)-induced obese mice were selected as a model.We investigated anti-adipogenic effects of RFG using MTS assay, Oil Red O Staining, real-time RT-PCR, western blot analysis, and immunofluorescence staining. The anti-obesity effect of RFG was confirmed in HFD-induced mice model using hematoxylin and eosin staining and serum analysis.RFG inhibited lipid accumulation in 3T3-L1 cells and hAMSCs by reducing expression of mammalian targets of rapamycin (mTOR), peroxisome proliferator-activated receptor (PPAR)γ, and CCAAT-enhancer binding protein (C/EBP)α. RFG phosphorylated AMP-activated protein kinase (AMPK) in a liver kinase B (LKB) 1-independent manner. Moreover, the anti-adipogenic effect of RFG was blocked by AMPK inhibitor. These results suggest that RFG inhibits lipid accumulation via AMPK signaling. Furthermore, RFG reduced the body weight, size of epididymal white adipose tissue (eWAT), and fatty liver in the mice. RFG also suppressed levels of adipogenic factors PPARγ, C/EBPα, FAS, LPL, and aP2) by activating AMPK in the eWAT and liver.RFG can ameliorate obesity, and thus, could be used as a therapeutic agent for treating obesity.