Bile acids are nutrient signaling hormones.
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.
['Zhou|Huiping|H|', 'Hylemon|Phillip B|PB|']
D001647:Bile Acids and Salts D005502:Food D005947:Glucose D006801:Humans D050356:Lipid Metabolism D008659:Metabolic Diseases D018160:Receptors, Cytoplasmic and Nuclear D043562:Receptors, G-Protein-Coupled D015398:Signal Transduction
Bile acids FXR PXR G-protein coupled receptor S1PR2 Insulin Liver AKT ERK1/2 small heterodimer partner SHP PKCζ non-alcoholic fatty liver disease NAFLD cholangiocarcinoma 12α-hydroxylase ASBT BSEP CA CCA CDCA CYP27A1 CYP7A1 CYP7B1 CYP8B1 DCA EGFR FGF15/19 G-6-Pase GCA GDCA GPCR Glucose metabolism HNF4a LCA LRH-1 LXR M1-5 NTCP P13K PEP carboxykinse PEPCK S1P Sphingosine 1-phosphate receptor 2 TCA apical sodium dependent transporter bile salt export protein (ABCB11) chenodeoxycholic acid cholesterol 7α-hydroxylase cholic acid deoxycholic acid epidermal growth factor receptor extracellular signal-regulated kinase farnesoid x receptor fibroblast growth factor 15/19 glucose-6-phosphatase glycocholic acid glycodeoxycholic acid hepatocyte nuclear factor 4 lithocholic acid liver X receptor liver-related homolog-1 muscarinic receptor 1-5 oxysterol 7α-hydroxylase phosphatidylinositol-3-kinase pregnane X receptor protein kinase B sodium taurocholate cotransporting polypeptide sphingosine 1-phosphate sphingosine 1-phosphate receptor 2 sterol 27-hydroxylase taurocholate