Journal article
Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.
- Kuhre RE Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Wewer Albrechtsen NJ Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Larsen O Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Jepsen SL Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Balk-Møller E Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Andersen DB Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Deacon CF Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Schoonjans K Laboratory of Metabolic Signaling, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH-1015, Lausanne, Switzerland.
- Reimann F 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.
- Gribble FM 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.
- Albrechtsen R Department of Biomedical Sciences, and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Hartmann B Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Rosenkilde MM Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
- Holst JJ 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.
- 2018-04-16
Published in:
- Molecular metabolism. - 2018
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
English
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.
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1016/j.molmet.2018.03.007
- PMID 29656109
- Persistent URL
- https://folia.unifr.ch/global/documents/150995
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