Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling.
Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling.
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DOI：
10.3390/ijms232113045
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发表时间：
2022-10-27
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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一种被称为非酒精性脂肪性肝病（NAFLD）的代谢性疾病影响着世界上四分之一以上的人口。胆汁酸（BA），作为参与脂质消化的去污剂，在NAFLD患者中显示出异常代谢。然而，BA也可以影响其他器官，例如大脑，在那里它具有神经保护作用。根据一系列研究，脑部疾病可能是NAFLD的肝外表现，如抑郁、脑血管系统改变和认知能力恶化。因此，我们认为NAFLD通过胆汁酸信号通路影响脑部疾病的发展。通过直接或间接的渠道，BAs可以向大脑发送信息。一些BA可以通过克服血脑屏障（BBB）直接作用于中央法尼醇X受体（FXR）和G蛋白胆汁酸激活受体1（GPBAR 1）。此外，胰高血糖素样肽-1（GLP-1）和成纤维细胞生长因子（FGF）19在激活后从肠FXR和GPBAR 1受体释放，两者都向大脑发送信号。肝脏和大脑中的炎性全身性代谢紊乱由胆汁酸激活的受体FXR和GPBAR 1调节，它们是潜在的治疗靶点。从胆汁酸的角度，我们研究了胆汁酸信号在NAFLD和脑部疾病中的变化。我们还建议开发双重GPBAR 1/FXR配体，以减少副作用并有效管理NAFLD和脑部疾病。
A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world’s population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood–brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.
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