Hylemon Phillip B, Takabe Kazuaki, Dozmorov Mikhail, Nagahashi Masayuki, Zhou Huiping
Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.
McGuire VA Medical Center, Richmond, VA 23249, USA.
Liver Res. 2017 Jun;1(1):10-16. doi: 10.1016/j.livres.2017.03.002. Epub 2017 Apr 26.
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.
胆汁酸（BA）在肝脏中由胆固醇合成。它们对于促进肠道中脂质、胆固醇和脂溶性维生素的吸收至关重要。胆汁酸是一类激素，可通过激活肝脏和肠道中的核受体（法尼酯X受体（FXR）、孕烷X受体、维生素D）和G蛋白偶联受体（如TGR5、鞘氨醇-1-磷酸受体2（S1PR2））来调节营养物质代谢。在肝脏中，结合型胆汁酸激活S1PR2可激活细胞外信号调节激酶1/2和AKT信号通路，以及细胞核鞘氨醇激酶2。后者产生鞘氨醇-1-磷酸（S1P），它是组蛋白脱乙酰酶1/2的抑制剂，可使参与固醇和脂质代谢的基因表达差异上调。我们在此讨论胆汁酸、FXR、胰岛素、S1P信号传导与营养物质代谢相互作用的新观点。
