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Reiner, J.* ; Mohebali, N.* ; Kurth, J.* ; Witte, M.* ; Prehn, C. ; Lindner, T.* ; Berlin, P.* ; Elleisy, N.* ; Förster, R.H.* ; Cecil, A. ; Jaster, R.* ; Adamski, J. ; Schwarzenböck, S.M.* ; Vollmar, B.* ; Krause, B.J.* ; Lamprecht, G.*

Glucagon-like peptide-2 pharmacotherapy activates hepatic Farnesoid X receptor-signaling to attenuate resection-associated bile acid loss in mice.

Mol. Metab. 95:102121 (2025)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The Glucagon-like peptide-2 (GLP-2) analogue teduglutide is used clinically for the treatment of short bowel syndrome and intestinal failure occurring after extensive intestinal resection. A recently discovered 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 well characterized. To study effects of teduglutide treatment, 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. 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, which was associated with induction of MAF BZIP Transcription Factor G. The data suggest that GLP-2-pharmacotherapy in mice significantly slows bile acid circulation primarily via hepatic Farnesoid X receptor-signaling.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Bile Acid Metabolome ; Cyp8b1 ; Glucagon-like Peptide-2 ; Ileocecal Resection ; Sehcat ; Short Bowel Syndrome; Short-bowel Syndrome; Growth-factor-i; Serum 7-alpha-hydroxy-4-cholesten-3-one; Malabsorption; Teduglutide; Proliferation
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 95, Heft: , Seiten: , Artikelnummer: 102121 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30505 - New Technologies for Biomedical Discoveries
30201 - Metabolic Health
Forschungsfeld(er) Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) A-630710-001
G-500600-001
Förderungen Rostock University Medical Center Clinician Scientist Program
Else Kroener-Fresenius-Stiftung
DOI 10.1016/j.molmet.2025.102121
WOS ID 001456891200001
Scopus ID 105000806729
PubMed ID 40097102
Erfassungsdatum 2025-03-20
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