Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease
文献类型：期刊论文
| 作者 | Jiao, Ting-ying2; Ma, Yuan-di1,2; Guo, Xiao-zhen2; Ye, Yun-fei1,2; Xie, Cen1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2022-02-25 |
| 页码 | 17 |
| ISSN号 | 1671-4083 |
| 关键词 | bile acids nonalcoholic fatty liver disease nonalcoholic steatohepatitis drug target Farnesoid X receptor G protein-coupled bile acid receptor |
| DOI | 10.1038/s41401-022-00880-z |
| 通讯作者 | Xie, Cen(xiecen@simm.ac.cn) |
| 英文摘要 | Nonalcoholic fatty liver disease (NAFLD), a series of liver metabolic disorders manifested by lipid accumulation within hepatocytes, has become the primary cause of chronic liver diseases worldwide. About 20%-30% of NAFLD patients advance to nonalcoholic steatohepatitis (NASH), along with cell death, inflammation response and fibrogenesis. The pathogenesis of NASH is complex and its development is strongly related to multiple metabolic disorders (e.g. obesity, type 2 diabetes and cardiovascular diseases). The clinical outcomes include liver failure and hepatocellular cancer. There is no FDA-approved NASH drug so far, and thus effective therapeutics are urgently needed. Bile acids are synthesized in hepatocytes, transported into the intestine, metabolized by gut bacteria and recirculated back to the liver by the enterohepatic system. They exert pleiotropic roles in the absorption of fats and regulation of metabolism. Studies on the relevance of bile acid disturbance with NASH render it as an etiological factor in NASH pathogenesis. Recent findings on the functional identification of bile acid receptors have led to a further understanding of the pathophysiology of NASH such as metabolic dysregulation and inflammation, and bile acid receptors are recognized as attractive targets for NASH treatment. In this review, we summarize the current knowledge on the role of bile acids and the receptors in the development of NAFLD and NASH, especially the functions of farnesoid X receptor (FXR) in different tissues including liver and intestine. The progress in the development of bile acid and its receptors-based drugs for the treatment of NASH including bile acid analogs and non-bile acid modulators on bile acid metabolism is also discussed. |
| WOS关键词 | FARNESOID-X-RECEPTOR ; SMALL HETERODIMER PARTNER ; VITAMIN-D-RECEPTOR ; TRANSPORTER INHIBITOR GSK2330672 ; INDUCED HEPATIC STEATOSIS ; URSODEOXYCHOLIC ACID ; NUCLEAR RECEPTOR ; PPAR-ALPHA ; LIPID-METABOLISM ; OBETICHOLIC ACID |
| 资助项目 | National Key Research and Development Program of China[2021YFA1301200] ; National Natural Science Foundation of China[82173873] ; National Natural Science Foundation of China[91957116] ; Shanghai Municipal Science and Technology Major Project ; Shanghai Rising-Star Program[20QA1411200] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | NATURE PUBL GROUP |
| WOS记录号 | WOS:000769534200002 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300236]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xie, Cen |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiao, Ting-ying,Ma, Yuan-di,Guo, Xiao-zhen,et al. Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease[J]. ACTA PHARMACOLOGICA SINICA,2022:17. |
| APA | Jiao, Ting-ying,Ma, Yuan-di,Guo, Xiao-zhen,Ye, Yun-fei,&Xie, Cen.(2022).Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease.ACTA PHARMACOLOGICA SINICA,17. |
| MLA | Jiao, Ting-ying,et al."Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease".ACTA PHARMACOLOGICA SINICA (2022):17. |
入库方式： OAI收割
来源：上海药物研究所
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