Dietary diosgenin transcriptionally down-regulated intestinal NPC1L1 expression to prevent cholesterol gallstone formation in mice

Journal of Biomedical Science

Research

Weiyi Shen¹  Gang Zhao¹  Bo Wang¹  Qihan Wang¹  Zhaoyan Jiang¹  Hai Hu¹  Wentao Shao²  Aihua Gu³ 

[1] Center of Gallstone Disease, Shanghai East Hospital, and Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai, China;Center of Gallstone Disease, Shanghai East Hospital, and Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai, China;State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China;Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China;State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China;Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China;

关键词: Gallstone;    Diosgenin;    Cholesterol;    NPC1L1;    Microbiome;   

DOI  :  10.1186/s12929-023-00933-3

 received in 2023-02-10, accepted in 2023-05-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCholesterol gallstone disease is a common disease. Reducing cholesterol burden is important to prevent/treat gallstone. In this study, we investigated the application of diosgenin (DG) to prevent the formation of gallstone in mice.MethodsAdult male C57BL/6J mice were fed with the lithogenic diet (LD) only or LD supplemented with DG or ezetimibe for 8 weeks. Incidences of gallstone formation were documented. Intestine and liver tissues were collected to measure the lipid contents and expression of genes in cholesterol metabolism. Caco2 cells were treated with DG to monitor the regulation on cholesterol absorption and the transcriptional regulation of Npc1l1 gene. Changes of gut microbiota by DG was analyzed. Intraperitoneal injection of LPS on mice was performed to verify its effects on STAT3 activation and Npc1l1 expression in the small intestine.ResultsLD led to 100% formation of gallstones in mice. In comparison, dietary DG or ezetimibe supplementary completely prevents gallstones formation. DG inhibited intestinal cholesterol absorption in mice as well as in Caco2 cells by down-regulation of Npc1l1 expression. DG could directly inhibit phosphorylation of STAT3 and its transcriptional regulation of Npc1l1 expression. Furthermore, DG could modulate gut microbiota profiles and LPS mediated STAT3 activation and Npc1l1 expression.ConclusionOur results demonstrated that dietary DG could inhibit intestinal cholesterol absorption through decreasing NPC1L1 expression to prevent cholesterol gallstone formation.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

40517_2023_252_Article_IEq31.gif

40517_2023_252_Article_IEq26.gif

Fig. 4

Fig. 1

Fig. 2

Fig. 2

Fig. 1

Fig. 9