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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)
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
ISSN (print) / ISBN
2212-8778
e-ISSN
2212-8778
Zeitschrift
Molecular Metabolism
Quellenangaben
Band: 95,
Artikelnummer: 102121
Verlag
Elsevier
Verlagsort
Amsterdam
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Förderungen
Rostock University Medical Center Clinician Scientist Program
Else Kroener-Fresenius-Stiftung
Else Kroener-Fresenius-Stiftung