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Bile acids as global regulators of hepatic nutrient metabolism

查看全文 作  者:Phillip [1,2]B.Hylemon;Kazuaki [3]Takabe;Mikhail [4]Dozmorov;Masayuki [5]Nagahashi;Huiping [1,2]Zhou 高影响力作者 机构地区:[1]Department of Microbiology and Immunology,Medical College of Virginia Campus,Virginia Commonwealth University,Richmond,VA,USA;[2]McGuire VA Medical Center,Richmond,VA,USA;[3]Department of Surgery,Medical College of Virginia Campus,Virginia Commonwealth University,Richmond,VA,USA;[4]Department of Biostatistics,Medical College of Virginia Campus,Virginia Commonwealth University,Richmond,VA,USA;[5]Department of Surgery,Niigata University,Japan高影响力机构 出  处:《Liver Research》索引2017年第1卷第1期,共7页高影响力期刊 基  金:This work was supported by the US National Institutes of Health(grants R01DK57543 and R01DK104893). 摘  要: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. 关 键 词:Sphingosine-1-phosphate Sphingosine kinase 2 Sphingosine-1-phosphate receptor 2 Fatty liver EPIGENETICS
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