Fig. 2.

Model of regulation of hepatic genes encoding enzymes involved in nutrient metabolism by conjugated bile acids and S1P. Conjugated bile acids and S1P activate S1PR2 and then activate nuclear SphK2 via cell signaling pathways such as AKT or ERK1/2 (8, 11, 54), increasing the levels of S1P in the nucleus. Nuclear S1P inhibits specific HDACs, causing an increase in acetylation of histones and upregulation of genes encoding nuclear receptors and enzymes involved in lipid and glucose metabolism. CBA, conjugated bile acid; Sph, sphingosine.