Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2029222 | Steroids | 2014 | 7 Pages |
Abstract
Bile salts play crucial roles in allowing the gastrointestinal system to digest, transport and metabolize nutrients. They function as nutrient signaling hormones by activating specific nuclear receptors (FXR, PXR, Vitamin D) and G-protein coupled receptors [TGR5, sphingosine-1 phosphate receptor 2 (S1PR2), muscarinic receptors]. Bile acids and insulin appear to collaborate in regulating the metabolism of nutrients in the liver. They both activate the AKT and ERK1/2 signaling pathways. Bile acid induction of the FXR-α target gene, small heterodimer partner (SHP), is highly dependent on the activation PKCζ, a branch of the insulin signaling pathway. SHP is an important regulator of glucose and lipid metabolism in the liver. One might hypothesize that chronic low grade inflammation which is associated with insulin resistance, may inhibit bile acid signaling and disrupt lipid metabolism. The disruption of these signaling pathways may increase the risk of fatty liver and non-alcoholic fatty liver disease (NAFLD). Finally, conjugated bile acids appear to promote cholangiocarcinoma growth via the activation of S1PR2.
Keywords
CYP8B1FXREGFRLXRBSEPNtcpCDCALRH-1HNF4ACYP27A1PEPCKGPCRGCACCAP13KCYP7B1CYP7A1NAFLDGDCAFGF15/19G-6-PaseDCAERK1/2farnesoid X receptorG-protein coupled receptorAsbtAktLCAsterol 27-hydroxylaseChenodeoxycholic acidDeoxycholic acidLithocholic acidCholic acidGlycodeoxycholic acidglycocholic acidoxysterol 7α-hydroxylasenon-alcoholic fatty liver diseaseFibroblast growth factor 15/19Hepatocyte nuclear factor 4phosphatidylinositol-3-kinaseprotein kinase Bsodium taurocholate cotransporting polypeptideliver X receptorCholangiocarcinomacholesterol 7α-hydroxylaseextracellular signal-regulated kinaseglucose-6-phosphataseEpidermal growth factor receptor
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Authors
Huiping Zhou, Phillip B. Hylemon,