Liver Research 2017;1(1):10-16
doi:10.1016/j.livres.2017.03.002
Bile acids as global regulators of hepatic nutrient metabolism
B.Hylemon PHILLIP 1 ; Takabe KAZUAKI ; Dozmorov MIKHAIL ; Nagahashi MASAYUKI ; Zhou HUIPING
Affiliations
Keywords
Sphingosine-1-phosphate; Sphingosine kinase 2; Sphingosine-1-phosphate receptor 2; Fatty liver; Epigenetics
Country
China
Language
Chinese
Abstract
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 al-lows 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.
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