Format

Send to

Choose Destination
Mol Metab. 2018 May;11:84-95. doi: 10.1016/j.molmet.2018.03.007. Epub 2018 Mar 17.

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

Author information

1
Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark.
2
Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
3
Laboratory of Metabolic Signaling, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH-1015, Lausanne, Switzerland.
4
Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, CB2 0QQ, United Kingdom.
5
Department of Biomedical Sciences, and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200, Copenhagen, Denmark.
6
Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark. Electronic address: jjholst@sund.ku.dk.

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.

KEYWORDS:

Bile-acids; GLP-1; Insulin; Neurotensin; PYY; TGR5

PMID:
29656109
PMCID:
PMC6001409
DOI:
10.1016/j.molmet.2018.03.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center