Bile acid-based therapies for non-alcoholic steatohepatitis and alcoholic Iiver disease

作     者：Tiangang Li John Y.L.Chiang Tiangang Li;John Y.L.Chiang

作者机构：Department of PharmacologyToxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKSUSA Department of Integrative Medical SciencesNortheast Ohio Medical UniversityRootstownOHUSA 

出 版 物：《Hepatobiliary Surgery and Nutrition》 (肝胆外科与营养（英文）)

年 卷 期：2020年第9卷第2期

页      面：152-169页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：This work was supported in part by NIH grants 1R01DK102487-01 and R01 DK117965-01A1 to T Li and DK44442 and DK58379 to JYL Chiang 

主　　题：Bile acid farnesoid X receptor(FXR) microbiota non-alcoholic steatohepatitis(NASH) alcoholic liver disease(ALD) 

摘      要：Bile acids are synthesized from cholesterol only in *** acids circulating in the enterohepatic system act as physiological detergent molecules to help solubilize biliary cholesterol and emulsify dietary lipids and fat-soluble vitamins in small *** acids are signaling molecules that activate nuclear receptor farnesoid X receptor(FXR)and cell surface G protein-coupled receptor *** critically regulates bile acid homeostasis by mediating bile acid feedback inhibition of hepatic bile acid *** addition,bile acid-activated cellular signaling pathways regulate metabolic homeostasis,immunity,and cell proliferation in various metabolically active *** the small and large intestine,gut bacterial enzymes modify primary bile acids to generate secondary bile acids to help shape the bile acid pool composition and subsequent biological *** turn,bile acids exhibit anti-microbial properties and modulate gut microbiota to influence host metabolism and ***,bile acid-based therapies including systemic and intestine-restricted FXR agonists,TGR5 agonists,fibroblast growth factor 19 analogue,intestine FXR antagonists,and intestine apical sodium-bile acid transporter(ASBT)inhibitors have been developed as promising treatments for non-alcoholic steatohepatitis(NASH).These pharmacological agents improved metabolic and inflammatory disorders via distinct mechanisms of action that are subjects of extensive research *** recently,human and experimental alcoholic liver disease(ALD)has been associated with disrupted bile acid *** additional,new findings showed that targeting bile acid metabolism and signaling may be promising therapeutic approaches for treating ALD.