Improving glucose and lipids metabolism: drug development based on bile acid related targets.
Improving glucose and lipids metabolism: drug development based on bile acid related targets.
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改善糖脂代谢：基于胆汁酸相关靶点的药物开发
DOI：
10.15698/cst2021.01.239
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发表时间：
2021-01-05
期刊：
影响因子：
6.4
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Shen H;Ding L;Baig M;Tian J;Wang Y;Huang W
减肥手术是治疗严重肥胖及其合并症的最有效的治疗方案之一。然而，这是一项重大手术，会带来一些副作用和风险，阻碍其临床应用。因此，迫切需要开发替代的更安全的药理学方法来模拟减肥手术。最近的研究表明，胆汁酸是介导减肥手术代谢益处的关键因素。胆汁酸可通过靶向胆汁酸核受体和膜受体（分别如FXR和TGR 5）而作为信号分子起作用。此外，胆汁酸的组成受肝固醇酶（如CYP 8B1）或肠道微生物组的调节。这些胆汁酸相关靶点都在调节代谢中发挥重要作用。基于这些靶点的药物开发可以为患者提供新的希望，而无需手术风险，成本更低。本文综述了胆汁酸相关靶点的最新研究进展以及基于这些靶点的小分子药物的研究进展。
Bariatric surgery is one of the most effective treatment options for severe obesity and its comorbidities. However, it is a major surgery that poses several side effects and risks which impede its clinical use. Therefore, it is urgent to develop alternative safer pharmacological approaches to mimic bariatric surgery. Recent studies suggest that bile acids are key players in mediating the metabolic benefits of bariatric surgery. Bile acids can function as signaling molecules by targeting bile acid nuclear receptors and membrane receptors, like FXR and TGR5 respectively. In addition, the composition of bile acids is regulated by either the hepatic sterol enzymes such as CYP8B1 or the gut microbiome. These bile acid related targets all play important roles in regulating metabolism. Drug development based on these targets could provide new hope for patients without the risks of surgery and at a lower cost. In this review, we summarize the most updated progress on bile acid related targets and development of small molecules as drug candidates based on these targets.