Bile acids as global regulators of hepatic nutrient metabolism.
Bile acids as global regulators of hepatic nutrient metabolism.
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DOI：
10.1016/j.livres.2017.03.002
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Zhou H
中科院分区：
文献类型：
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作者：
Hylemon PB;Takabe K;Dozmorov M;Nagahashi M;Zhou H
胆汁酸 (BA) 由肝脏中的胆固醇合成。它们对于促进肠道吸收脂质、胆固醇和脂溶性维生素至关重要。 BA 是通过激活肝脏和肠道中的核受体（法呢醇 X 受体 (FXR)、孕烷 X 受体、维生素 D）和 G 蛋白偶联受体（例如 TGR5、1-磷酸鞘氨醇受体 2 (S1PR2)）来调节营养代谢的激素。在肝脏中，结合 BA 激活 S1PR2 会激活细胞外信号调节激酶 1/2 和 AKT 信号通路以及核鞘氨醇激酶 2。后者产生 1-磷酸鞘氨醇 (S1P)，一种组蛋白脱乙酰酶 1/2 的抑制剂，可差异性上调参与甾醇和脂质代谢的基因的表达。我们在此讨论 BA、FXR、胰岛素、S1P 信号传导和营养代谢相互作用的新兴概念。
Bile acids (BA) are synthesized from cholesterol in the liver. They are essential for promotion of the absorption of lipids, cholesterol, and lipid-soluble vitamins from the intestines. BAs are hormones that regulate nutrient metabolism by activating nuclear receptors (farnesoid X receptor (FXR), pregnane X receptor, vitamin D) and G protein-coupled receptors (e.g., TGR5, sphingosine-1-phosphate receptor 2 (S1PR2)) in the liver and intestines. In the liver, S1PR2 activation by conjugated BAs activates the extracellular signal-regulated kinase 1/2 and AKT signaling pathways, and nuclear sphingosine kinase 2. The latter produces sphingosine-1-phosphate (S1P), an inhibitor of histone deacetylases 1/2, which allows for the differential up-regulation of expression of genes involved in the metabolism of sterols and lipids. We discuss here the emerging concepts of the interactions of BAs, FXR, insulin, S1P signaling and nutrient metabolism.