红曲麦角固醇-6-β-龙胆二糖苷通过调节 AMPK/mTOR 信号通路抑制脂质积累和体重增加。

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

机构信息

Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea.

Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Republic of Korea; Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.

出版信息

Phytomedicine. 2019 Sep;62:152952. doi: 10.1016/j.phymed.2019.152952. Epub 2019 May 9.

DOI:10.1016/j.phymed.2019.152952

PMID:31132754

Abstract

BACKGROUND

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.

PURPOSE

The aim of this study was to examine whether RFG can ameliorate obesity and the mechanism of lipid accumulation regulated by RFG.

STUDY DESIGN

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.

METHODS

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.

RESULTS

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.

CONCLUSION

RFG can ameliorate obesity, and thus, could be used as a therapeutic agent for treating obesity.

摘要

背景

山扁豆苦苷-6-β-龙胆二糖苷（RFG）是鸡矢藤种子的一种成分，可能具有调节高血脂的作用，但它的抗肥胖作用及其相关机制尚未阐明。

目的

本研究旨在探讨 RFG 是否能改善肥胖以及 RFG 调节脂质积累的机制。

研究设计

在体外实验中，我们使用 3T3-L1 细胞和人脂肪间充质干细胞（hAMSCs）证实了 RFG 的抗脂肪生成作用。为了证实其抗肥胖作用，我们选择高脂饮食（HFD）诱导的肥胖小鼠作为模型。

方法

我们通过 MTS 检测、油红 O 染色、实时 RT-PCR、Western blot 分析和免疫荧光染色来研究 RFG 的抗脂肪生成作用。通过苏木精和伊红染色以及血清分析来确认 RFG 在 HFD 诱导的肥胖小鼠模型中的抗肥胖作用。

结果

RFG 通过降低哺乳动物雷帕霉素靶蛋白（mTOR）、过氧化物酶体增殖物激活受体（PPAR）γ和 CCAAT 增强子结合蛋白（C/EBP）α的表达来抑制 3T3-L1 细胞和 hAMSCs 中的脂质积累。RFG 以 LKB1 非依赖性方式磷酸化 AMP 激活的蛋白激酶（AMPK）。此外，AMPK 抑制剂阻断了 RFG 的抗脂肪生成作用。这些结果表明，RFG 通过 AMPK 信号通路抑制脂质积累。此外，RFG 降低了小鼠的体重、附睾白色脂肪组织（eWAT）的大小和脂肪肝。RFG 还通过在 eWAT 和肝脏中激活 AMPK 来抑制脂肪生成因子 PPARγ、C/EBPα、FAS、LPL 和 aP2 的水平。