Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice
Objective: Villus growth in the small bowel by Glucagon-like peptide-2 (GLP-2) pharmacotherapy improves intestinal absorption capacity and is now used clinically for the treatment of short bowel syndrome and intestinal failure occurring after extensive intestinal resection. Another recently acknowle...
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Elsevier
2025-05-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877825000286 |
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| author | Johannes Reiner Nooshin Mohebali Jens Kurth Maria Witte Cornelia Prehn Tobias Lindner Peggy Berlin Nagi Elleisy Robert H. Förster Alexander Cecil Robert Jaster Jerzy Adamski Sarah M. Schwarzenböck Brigitte Vollmar Bernd J. Krause Georg Lamprecht |
| author_facet | Johannes Reiner Nooshin Mohebali Jens Kurth Maria Witte Cornelia Prehn Tobias Lindner Peggy Berlin Nagi Elleisy Robert H. Förster Alexander Cecil Robert Jaster Jerzy Adamski Sarah M. Schwarzenböck Brigitte Vollmar Bernd J. Krause Georg Lamprecht |
| author_sort | Johannes Reiner |
| collection | DOAJ |
| description | Objective: Villus growth in the small bowel by Glucagon-like peptide-2 (GLP-2) pharmacotherapy improves intestinal absorption capacity and is now used clinically for the treatment of short bowel syndrome and intestinal failure occurring after extensive intestinal resection. Another recently acknowledged effect of GLP-2 treatment is the inhibition of gallbladder motility and increased gallbladder refilling. However, the impact of these two GLP-2-characteristic effects on bile acid metabolism in health and after intestinal resection is not understood. Methods: Mice were injected with the GLP-2-analogue teduglutide or vehicle. We combined the selenium-75-homocholic acid taurine (SeHCAT) assay with novel spatial imaging in healthy mice and after ileocecal resection (ICR mice) and associated the results with clinical stage targeted bile acid metabolomics as well as gene expression analyses. Results: ICR mice had virtual complete intestinal loss of secondary bile acids, and an increased ratio of 12α-hydroxylated vs. non-12α-hydroxylated bile acids, which was attenuated by teduglutide. Teduglutide promoted SeHCAT retention in healthy and in ICR mice. Acute concentration of the SeHCAT-signal into the hepatobiliary system was observed. Teduglutide induced significant repression of hepatic cyp8b1 expression, likely by induction of MAF BZIP Transcription Factor G. Conclusions: The data suggest that GLP-2-pharmacotherapy in mice significantly slows bile acid circulation primarily via hepatic Farnesoid X receptor-signaling. |
| format | Article |
| id | doaj-art-728a36a6db044699b52f3a5293cd7540 |
| institution | OA Journals |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-728a36a6db044699b52f3a5293cd75402025-08-20T01:54:15ZengElsevierMolecular Metabolism2212-87782025-05-019510212110.1016/j.molmet.2025.102121Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in miceJohannes Reiner0Nooshin Mohebali1Jens Kurth2Maria Witte3Cornelia Prehn4Tobias Lindner5Peggy Berlin6Nagi Elleisy7Robert H. Förster8Alexander Cecil9Robert Jaster10Jerzy Adamski11Sarah M. Schwarzenböck12Brigitte Vollmar13Bernd J. Krause14Georg Lamprecht15Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, Germany; Corresponding author. Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Germany.Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, GermanyDepartment of Nuclear Medicine, Rostock University Medical Center, Rostock, GermanyDepartment of General, Visceral, Thoracic, Vascular and Transplant Surgery, Rostock University Medical Center, 18057 Rostock, GermanyMetabolomics and Proteomics Core (MPC), Helmholtz Zentrum München, GermanyCore Facility Multimodal Small Animal Imaging, Rostock University Medical Center, Rostock, GermanyDivision of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, GermanyDivision of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, GermanyDivision of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, GermanyMetabolomics and Proteomics Core (MPC), Helmholtz Zentrum München, GermanyDivision of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, GermanyMetabolomics and Proteomics Core (MPC), Helmholtz Zentrum München, GermanyDepartment of Nuclear Medicine, Rostock University Medical Center, Rostock, GermanyRudolf-Zenker-Institute for Experimental Surgery, Rostock University Medical Center, 18057 Rostock, GermanyDepartment of Nuclear Medicine, Rostock University Medical Center, Rostock, GermanyDivision of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, Rostock, GermanyObjective: Villus growth in the small bowel by Glucagon-like peptide-2 (GLP-2) pharmacotherapy improves intestinal absorption capacity and is now used clinically for the treatment of short bowel syndrome and intestinal failure occurring after extensive intestinal resection. Another recently acknowledged effect of GLP-2 treatment is the inhibition of gallbladder motility and increased gallbladder refilling. However, the impact of these two GLP-2-characteristic effects on bile acid metabolism in health and after intestinal resection is not understood. Methods: Mice were injected with the GLP-2-analogue teduglutide or vehicle. We combined the selenium-75-homocholic acid taurine (SeHCAT) assay with novel spatial imaging in healthy mice and after ileocecal resection (ICR mice) and associated the results with clinical stage targeted bile acid metabolomics as well as gene expression analyses. Results: ICR mice had virtual complete intestinal loss of secondary bile acids, and an increased ratio of 12α-hydroxylated vs. non-12α-hydroxylated bile acids, which was attenuated by teduglutide. Teduglutide promoted SeHCAT retention in healthy and in ICR mice. Acute concentration of the SeHCAT-signal into the hepatobiliary system was observed. Teduglutide induced significant repression of hepatic cyp8b1 expression, likely by induction of MAF BZIP Transcription Factor G. Conclusions: The data suggest that GLP-2-pharmacotherapy in mice significantly slows bile acid circulation primarily via hepatic Farnesoid X receptor-signaling.http://www.sciencedirect.com/science/article/pii/S2212877825000286Glucagon-like peptide-2Bile acid metabolomecyp8b1SeHCATShort bowel syndromeIleocecal resection |
| spellingShingle | Johannes Reiner Nooshin Mohebali Jens Kurth Maria Witte Cornelia Prehn Tobias Lindner Peggy Berlin Nagi Elleisy Robert H. Förster Alexander Cecil Robert Jaster Jerzy Adamski Sarah M. Schwarzenböck Brigitte Vollmar Bernd J. Krause Georg Lamprecht Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice Molecular Metabolism Glucagon-like peptide-2 Bile acid metabolome cyp8b1 SeHCAT Short bowel syndrome Ileocecal resection |
| title | Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice |
| title_full | Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice |
| title_fullStr | Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice |
| title_full_unstemmed | Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice |
| title_short | Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice |
| title_sort | glucagon like peptide 2 pharmacotherapy activates hepatic farnesoid x receptor signaling to attenuate resection associated bile acid loss in mice |
| topic | Glucagon-like peptide-2 Bile acid metabolome cyp8b1 SeHCAT Short bowel syndrome Ileocecal resection |
| url | http://www.sciencedirect.com/science/article/pii/S2212877825000286 |
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