Bile acids are nutrient signaling hormones

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.

3,4-Seco-12α-hydroxy-5β-cholan-3,4,24-trioic Acid, a Novel Secondary Bile Acid: Isolation from the Bile of the Common Ringtail Possum (Pseudocheirus peregrinus) and Chemical Synthesis

“…Oxidative cleavage of compound 2 with sodium periodate [11,12] and subsequent treatment of the resulting product with Jones reagent resulted in simultaneous dicarboxylation at C-3 and C-4 to give 3,4-seco-12α-acetoxy-5β-cholan-3,4,24-trioic acid 24-methyl ester (3). Alkaline hydrolysis of the 3 followed by acidification afforded the desired 3,4,24-trioic acid (1).…”

“…In the small intestine, bile acids solubilize dietary lipids, and in the large intestine, modulate water and electrolyte movement [1,2]. In addition, in the past decade, bile acids have been shown to also possess potent and important signaling properties [3]. Bile acids modulate the expression of multiple genes via the nuclear receptor FXR (farnesoid X receptor) that is activated by bile acids.…”

Taurocholic acid metabolism by gut microbes and colon cancer

“…[15][16][17] Bile acids have become recognized as a particularly important class of steroid molecule regulating host and microbial physiology. [18][19][20] The gut microbiota have the capacity to significantly alter the physicochemical properties of bile acids, generating high affinity ligands to host nuclear receptors (farnesoid X receptor, Vitamin D receptor (VDR), pregnane X receptor) and G-coupled protein receptors (TGR-5), in addition to sphingosine-1-phosphate receptor 2, and activate a range of signal transduction pathways (JNK, ERK, Akt). 19,20 The levels and composition of the human bile acid pool affects gut microbiome structure, and gut microbiome structure and gene content affects bile acid pool composition.…”

“…[18][19][20] The gut microbiota have the capacity to significantly alter the physicochemical properties of bile acids, generating high affinity ligands to host nuclear receptors (farnesoid X receptor, Vitamin D receptor (VDR), pregnane X receptor) and G-coupled protein receptors (TGR-5), in addition to sphingosine-1-phosphate receptor 2, and activate a range of signal transduction pathways (JNK, ERK, Akt). 19,20 The levels and composition of the human bile acid pool affects gut microbiome structure, and gut microbiome structure and gene content affects bile acid pool composition. The antimicrobial nature of bile acids prevents bacterial overgrowth in the small intestine; however, microbial metabolism of bile salts in the large intestine represents long-term exposure to metabolic end-products that are implicated in CRC.…”

Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial

“…Bile acids (BAs) participate in the control of glucose and lipid metabolism and energy homeostasis [6][7][8]. They act as signaling hormones by activating nuclear receptors and membrane coupled receptors in the intestine, liver, muscle and adipose tissue.…”