{"title":"Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development.","authors":"Tiangang Li, John Y L Chiang","doi":"10.1124/pharmrev.124.000978","DOIUrl":null,"url":null,"abstract":"<p><p>Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders. SIGNIFICANCE STATEMENT: Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling holds promise for treating metabolic and inflammatory diseases.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":null,"pages":null},"PeriodicalIF":19.3000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549937/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacological Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1124/pharmrev.124.000978","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders. SIGNIFICANCE STATEMENT: Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling holds promise for treating metabolic and inflammatory diseases.
胆汁酸是胆固醇分解代谢的最终产物。肝脏合成的胆汁酸占人体每日胆固醇周转量的大部分。胆汁分泌胆汁酸可产生胆汁流,促进胆汁分泌脂质、内源性代谢物和异种生物。在肠道中,胆汁酸可促进食物中脂类和脂溶性维生素的消化和吸收。胆汁酸通过激活核受体和 G 蛋白偶联受体以及与肠道微生物群的相互作用,对宿主的新陈代谢以及先天性和适应性免疫进行重要调节,并参与胆汁淤积症、代谢功能障碍相关性脂肪肝(MASLD)、酒精相关性肝病(ALD)、2 型糖尿病和炎症性肠病(IBD)的发病机制。胆汁酸及其衍生物已被开发为治疗慢性代谢性和炎症性肝病以及胃肠道疾病的潜在治疗药物。意义声明 胆汁酸可促进胆汁中胆固醇的溶解和饮食中脂质的吸收,调节宿主代谢和免疫,并调节肠道微生物组。以胆汁酸代谢和信号传导为靶点,有望治疗代谢性和炎症性疾病。
期刊介绍:
Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.