Bile Acid Signaling Pathways from the Enterohepatic Circulation to the Central Nervous System.
Bile Acid Signaling Pathways from the Enterohepatic Circulation to the Central Nervous System.
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DOI：
10.3389/fnins.2017.00617
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发表时间：
2017
影响因子：
4.3
通讯作者：
Eggink HM
中科院分区：
文献类型：
--
作者：
Mertens KL;Kalsbeek A;Soeters MR;Eggink HM
胆汁酸是最广为人知的与脂肪消化有关的去污剂。此外，过去十年的新数据表明，胆汁酸还可以作为肠道激素，通过FXR(法尼醇X受体)和TGR5(武田G蛋白偶联受体5)等受体影响代谢过程。胆汁酸的这些作用不仅限于胃肠道，还可以影响整个生物体的不同组织。目前尚不清楚这些效应是否也涉及胆汁酸对中枢神经系统(CNS)的信号传递。胆汁酸对中枢神经系统的信号传导包括直接途径和间接途径。胆汁酸可以通过中枢FXR和TGR5信号直接在大脑中发挥作用。此外，还有两条间接途径，涉及与肠道胆汁酸受体相互作用时释放的中间体。肠道FXR和TGR5受体的激活可导致成纤维细胞生长因子19(FGF19)和胰升糖素样肽1(GLP-1)的释放，两者都能向中枢神经系统传递信号。我们的结论是，当血浆胆汁酸水平较高时，所有这三条途径都可能参与中枢神经系统的信号传递。然而，在正常的生理环境下，涉及GLP-1的间接途径可能在大脑中引起最实质性的影响。
Bile acids are best known as detergents involved in the digestion of lipids. In addition, new data in the last decade have shown that bile acids also function as gut hormones capable of influencing metabolic processes via receptors such as FXR (farnesoid X receptor) and TGR5 (Takeda G protein-coupled receptor 5). These effects of bile acids are not restricted to the gastrointestinal tract, but can affect different tissues throughout the organism. It is still unclear whether these effects also involve signaling of bile acids to the central nervous system (CNS). Bile acid signaling to the CNS encompasses both direct and indirect pathways. Bile acids can act directly in the brain via central FXR and TGR5 signaling. In addition, there are two indirect pathways that involve intermediate agents released upon interaction with bile acids receptors in the gut. Activation of intestinal FXR and TGR5 receptors can result in the release of fibroblast growth factor 19 (FGF19) and glucagon-like peptide 1 (GLP-1), both capable of signaling to the CNS. We conclude that when plasma bile acids levels are high all three pathways may contribute in signal transmission to the CNS. However, under normal physiological circumstances, the indirect pathway involving GLP-1 may evoke the most substantial effect in the brain.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1152/ajpendo.00035.2004
发表时间：
2004-07-01
影响因子：
5.1
作者：
Dardevet, D;Moore, MC;Cherrington, AD
通讯作者：
Cherrington, AD
影响因子：
4.8
作者：
Abe, T;Kakyo, M;Yawo, H
通讯作者：
Yawo, H
影响因子：
24.5
作者：
ANGELIN, B;BJORKHEM, I
通讯作者：
BJORKHEM, I
影响因子：
24.5
作者：
BRON, B;WALDRAM, R;WILLIAMS, R
通讯作者：
WILLIAMS, R