Da Silva Lima, N.* ; Cabaleiro, A.* ; Novoa, E.* ; Riobello, C.* ; Knerr, P.J.* ; He, Y.* ; Esquinas-Román, E.M.* ; González-García, I.* ; Prévot, V.* ; Schwaninger, M.* ; Dieguez, C.* ; López, M.* ; Müller, T.D. ; Varela-Rey, M.* ; Douros, J.D.* ; Nogueiras, R.*
GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells.
Cell. Mol. Life Sci. 81:468 (2024)
The use of incretin agonists for managing metabolic dysfunction-associated steatohepatitis (MASH) is currently experiencing considerable interest. However, whether these compounds have a direct action on MASH is still under debate. This study aims to investigate whether GLP-1R/GIPR agonists act directly in hepatocytes and hepatic stellate cells (HSCs). For this, human hepatocyte and HSCs lines, as well as primary human hepatocytes and HSCs treated with Liraglutide, Acyl-GIP or the GLP-1/GIP dual agonist (MAR709) were used. We show that the concentrations of each compound, which were effective in insulin release, did not induce discernible alterations in either hepatocytes or HSCs. In hepatocytes displaying elevated fatty acid content after the treatment with oleic acid and palmitic acid, none of the three compounds reduced lipid concentration. Similarly, in HSCs activated with transforming growth factor-β (TGFb), Liraglutide, Acyl-GIP and MAR709 failed to ameliorate the elevated expression of fibrotic markers. The three compounds were also ineffective in phosphorylating CREB, which mediates insulinotropic actions, in both hepatocytes and HSCs. These findings indicate that incretin agonists have no direct actions in human hepatocytes or hepatic stellate cells, suggesting that their beneficial effects in patients with MASH are likely mediated indirectly, potentially through improvements in body weight, insulin resistance and glycemic control.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Fatty Acids ; Gipr ; Glp-1r ; Liver Fibrosis; Inhibitory Polypeptide Receptor; Insulin-resistance; Weight-loss; High-fat; Expression; Glucagon; Disturbances; Fibrosis; Obesity; Mice
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2024
Prepublished im Jahr
0
HGF-Berichtsjahr
2024
ISSN (print) / ISBN
1420-682X
e-ISSN
1420-9071
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 81,
Heft: 1,
Seiten: ,
Artikelnummer: 468
Supplement: ,
Reihe
Verlag
Birkhäuser
Verlagsort
Picassoplatz 4, Basel, 4052, Switzerland
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-501900-221
Förderungen
Ministerio de Ciencia e Innovacin
Copyright
Erfassungsdatum
2024-12-04