Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas
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 pancre...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Molecular Metabolism |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877818301194 |
| _version_ | 1818543187943227392 |
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| author | Rune E. Kuhre Nicolai J. Wewer Albrechtsen Olav Larsen Sara L. Jepsen Emilie Balk-Møller Daniel B. Andersen Carolyn F. Deacon Kristina Schoonjans Frank Reimann Fiona M. Gribble Reidar Albrechtsen Bolette Hartmann Mette M. Rosenkilde Jens J. Holst |
| author_facet | Rune E. Kuhre Nicolai J. Wewer Albrechtsen Olav Larsen Sara L. Jepsen Emilie Balk-Møller Daniel B. Andersen Carolyn F. Deacon Kristina Schoonjans Frank Reimann Fiona M. Gribble Reidar Albrechtsen Bolette Hartmann Mette M. Rosenkilde Jens J. Holst |
| author_sort | Rune E. Kuhre |
| collection | DOAJ |
| description | 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, Neurotensin, Insulin, PYY, TGR5 |
| first_indexed | 2024-12-11T22:32:03Z |
| format | Article |
| id | doaj.art-7e8b0269704c40bea7389e41b44cde95 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-11T22:32:03Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-7e8b0269704c40bea7389e41b44cde952022-12-22T00:48:05ZengElsevierMolecular Metabolism2212-87782018-05-01118495Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreasRune E. Kuhre0Nicolai J. Wewer Albrechtsen1Olav Larsen2Sara L. Jepsen3Emilie Balk-Møller4Daniel B. Andersen5Carolyn F. Deacon6Kristina Schoonjans7Frank Reimann8Fiona M. Gribble9Reidar Albrechtsen10Bolette Hartmann11Mette M. Rosenkilde12Jens J. Holst13Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, DenmarkLaboratory of Metabolic Signaling, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH-1015, Lausanne, SwitzerlandMetabolic 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 KingdomMetabolic 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 KingdomDepartment of Biomedical Sciences, and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark; NNF Center for Basic Metabolic Research, University of Copenhagen, DK-2200, Copenhagen, Denmark; Corresponding author. Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Panum Institute, Blegdamsvej 3B, 12.2, DK-2200, Copenhagen N, Denmark.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, Neurotensin, Insulin, PYY, TGR5http://www.sciencedirect.com/science/article/pii/S2212877818301194 |
| spellingShingle | Rune E. Kuhre Nicolai J. Wewer Albrechtsen Olav Larsen Sara L. Jepsen Emilie Balk-Møller Daniel B. Andersen Carolyn F. Deacon Kristina Schoonjans Frank Reimann Fiona M. Gribble Reidar Albrechtsen Bolette Hartmann Mette M. Rosenkilde Jens J. Holst Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas Molecular Metabolism |
| title | Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas |
| title_full | Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas |
| title_fullStr | Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas |
| title_full_unstemmed | Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas |
| title_short | Bile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas |
| title_sort | bile acids are important direct and indirect regulators of the secretion of appetite and metabolism regulating hormones from the gut and pancreas |
| url | http://www.sciencedirect.com/science/article/pii/S2212877818301194 |
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