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Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.

Published version
Peer-reviewed

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Authors

Kuhre, Rune E 
Wewer Albrechtsen, Nicolai J 
Larsen, Olav 
Jepsen, Sara L 
Balk-Møller, Emilie 

Abstract

OBJECTIVE: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. METHODS: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose. The molecular mechanisms that underlie the secretion was studied by isolated perfused rat and mouse small intestine and pancreas preparations and supported by immunohistochemistry, expression analysis, and pharmacological studies. RESULTS: Bile acids robustly stimulate secretion of not only the incretin hormones, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP-1), but also glucagon and insulin in vivo, to levels comparable to those resulting from glucose stimulation. The mechanisms of GLP-1, neurotensin, and peptide YY (PYY) secretion was secondary to intestinal absorption and depended on activation of basolateral membrane Takeda G-protein receptor 5 (TGR5) receptors on the L-cells in the following order of potency: Lithocholic acid (LCA) >Deoxycholicacid (DCA)>Chenodeoxycholicacid (CDCA)> Cholic acid (CA). Thus BAs did not stimulate secretion of GLP-1 and PYY from perfused small intestine in TGR5 KO mice but stimulated robust responses in wild type littermates. TGR5 is not expressed on α-cells or β-cells, and BAs had no direct effects on glucagon or insulin secretion from the perfused pancreas. CONCLUSION: BAs should be considered not only as fat emulsifiers but also as important regulators of appetite- and metabolism-regulating hormones by activation of basolateral intestinal TGR5.

Description

Keywords

Bile-acids, GLP-1, Insulin, Neurotensin, PYY, TGR5, Animals, Bile Acids and Salts, COS Cells, Cells, Cultured, Chlorocebus aethiops, Gastric Inhibitory Polypeptide, Glucagon-Like Peptide 1, Intestinal Mucosa, Male, Mice, Mice, Inbred C57BL, Pancreas, Peptide YY, Rats, Rats, Wistar, Receptors, G-Protein-Coupled

Journal Title

Mol Metab

Conference Name

Journal ISSN

2212-8778
2212-8778

Volume Title

11

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_UU_12012/3)
Wellcome Trust (106262/Z/14/Z)
European Commission (266408)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)