The triterpenoid sapogenin (2 alpha-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling

doi:10.1038/s41419-020-02974-0

	The triterpenoid sapogenin (2 alpha-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling
	Xie, Zhifu 1; Jiang, Haowen 1; Liu, Wei 1,2; Zhang, Xinwen 1; Chen, Dakai 1; Sun, Shuimei 1,2; Zhou, Chendong 1; Liu, Jia 1; Bao, Sheng 3; Wang, Xiachang 3
刊名	CELL DEATH & DISEASE
	2020-09-17
卷号	11 期号:9 页码:10
ISSN号	2041-4889
DOI	10.1038/s41419-020-02974-0
通讯作者	Hu, Lihong(lhhu@njucm.edu.cn) ; Li, Jingya(jyli@simm.ac.cn)
英文摘要	Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2 alpha -OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-beta -muricholic acid (T beta MCA) in the intestine. T beta MCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal T beta MCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.
资助项目	China Postdoctoral Science Foundation[2018M632186] ; National Natural Science Foundation of China[81803596] ; National Natural Science Foundation of China[81673493] ; Specialised Plan for Major New Drug Creation[2018ZX09711002-016] ; Natural science foundation of Jiangsu Higher Education Institutions[17KJA360004] ; Natural science foundation of Jiangsu Higher Education Institutions[18KJA360010] ; Programme for Outstanding Scientific and Technological Innovation Team of Jiangsu Higher Education Institutions ; Priority Academic Programme Development of Jiangsu Higher Education Institutions
WOS关键词	GLUCAGON-LIKE PEPTIDE-1 ; BILE-ACID METABOLISM ; FXR ; RECEPTORS ; SECRETION ; GROWTH ; LIVER
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000574542300006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291317]
专题	中国科学院上海药物研究所
通讯作者	Hu, Lihong; Li, Jingya
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100864, Peoples R China 3.Nanjing Univ Chinese Med, Jiangsu Key Lab Funct Subst Chinese Med, Nanjing 210023, Peoples R China
推荐引用方式 GB/T 7714	Xie, Zhifu,Jiang, Haowen,Liu, Wei,et al. The triterpenoid sapogenin (2 alpha-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling[J]. CELL DEATH & DISEASE,2020,11(9):10.
APA	Xie, Zhifu.,Jiang, Haowen.,Liu, Wei.,Zhang, Xinwen.,Chen, Dakai.,...&Li, Jingya.(2020).The triterpenoid sapogenin (2 alpha-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling.CELL DEATH & DISEASE,11(9),10.
MLA	Xie, Zhifu,et al."The triterpenoid sapogenin (2 alpha-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling".CELL DEATH & DISEASE 11.9(2020):10.