Enterohepatic and non-canonical roles of farnesoid X receptor in controlling lipid and glucose metabolism.
Enterohepatic and non-canonical roles of farnesoid X receptor in controlling lipid and glucose metabolism.
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DOI：
10.1016/j.mce.2022.111616
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发表时间：
2022-06-01
影响因子：
4.1
通讯作者：
Anakk, Sayeepriyadarshini
中科院分区：
文献类型：
--
作者：
Zhou, Weinan;Anakk, Sayeepriyadarshini
法尼醇X受体（Farnesoid X receptor，FXR）是一种转录调节胆汁酸稳态的核受体，沿着营养物质代谢。除了胃肠道（GI）之外，FXR表达还广泛见于肾脏、肾上腺、胰腺、脂肪、骨骼肌、心脏和脑。除了肝脏和肠道，FXR信号传导在其他组织代谢中的相关性仍然知之甚少。本文综述了FXR在正常和疾病状态下调节胆汁酸、脂质和葡萄糖稳态的经典和非经典组织特异性作用。据报道，FXR激活可预防胆汁淤积、非酒精性脂肪肝病（NAFLD）、非酒精性脂肪性肝炎（NASH）、2型糖尿病、心血管和肾脏疾病。几项正在进行的临床试验正在研究FXR配体作为原发性胆汁性胆管炎（PBC）和NASH的治疗靶点，这证实了FXR信号传导在调节代谢过程中的重要性。这篇综述强调了FXR配体，尽管是治疗代谢性疾病的有吸引力的治疗靶点，但FXR的组织特异性调节可能是克服一些不良临床效应的关键。
Farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates bile acid homeostasis along with nutrient metabolism. In addition to the gastrointestinal (GI) tract, FXR expression has been widely noted in kidneys, adrenal glands, pancreas, adipose, skeletal muscle, heart, and brain. Except for the liver and gut, the relevance of FXR signaling in metabolism in other tissues remains poorly understood. This review examines the classical and non-canonical tissue-specific roles of FXR in regulating bile acids, lipids, and glucose homeostasis under normal and diseased states. FXR activation has been reported to be protective against cholestasis, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), type 2 diabetes, cardiovascular and kidney diseases. Several ongoing clinical trials are investigating FXR ligands as a therapeutic target for primary biliary cholangitis (PBC) and NASH, which substantiate the significance of FXR signaling in modulating metabolic processes. This review highlights that FXR ligands, albeit an attractive therapeutic target for treating metabolic diseases, tissue-specific modulation of FXR may be the key to overcoming some of the adverse clinical effects.
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DOI：
10.1016/j.jcmgh.2021.01.012
发表时间：
2021
影响因子：
7.2
作者：
Cariello M;Piccinin E;Moschetta A
通讯作者：
Moschetta A
DOI：
10.1002/hep.29305
发表时间：
2017-12
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
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通讯作者：
Anakk S
影响因子：
29.4
作者：
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通讯作者：
Karpen, SJ
影响因子：
4.8
作者：
Chen, F;Ma, L;Shneider, BL
通讯作者：
Shneider, BL
影响因子：
4.8
作者：
Bhatnagar, Sushant;Damron, Holly A.;Hillgartner, F. Bradley
通讯作者：
Hillgartner, F. Bradley