Bile acids are nutrient signaling hormones

Steroids. 2014 Aug:86:62-8. doi: 10.1016/j.steroids.2014.04.016. Epub 2014 May 10.

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: 12α-hydroxylase; AKT; ASBT; BSEP; Bile acids; CA; CCA; CDCA; CYP27A1; CYP7A1; CYP7B1; CYP8B1; DCA; EGFR; ERK1/2; FGF15/19; FXR; G-6-Pase; G-protein coupled receptor; GCA; GDCA; GPCR; Glucose metabolism; HNF4a; Insulin; LCA; LRH-1; LXR; Liver; M1-5; NAFLD; NTCP; P13K; PEP carboxykinse; PEPCK; PKCζ; PXR; S1P; S1PR2; SHP; Sphingosine 1-phosphate receptor 2; TCA; apical sodium dependent transporter; bile salt export protein (ABCB11); chenodeoxycholic acid; cholangiocarcinoma; 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; non-alcoholic fatty liver disease; oxysterol 7α-hydroxylase; phosphatidylinositol-3-kinase; pregnane X receptor; protein kinase B; small heterodimer partner; sodium taurocholate cotransporting polypeptide; sphingosine 1-phosphate; sphingosine 1-phosphate receptor 2; sterol 27-hydroxylase; taurocholate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Bile Acids and Salts / blood
  • Bile Acids and Salts / metabolism*
  • Food*
  • Glucose / metabolism
  • Humans
  • Lipid Metabolism
  • Metabolic Diseases / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction*

Substances

  • Bile Acids and Salts
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • Glucose