Efficacy of fibroblast growth factor 21 in non-alcoholic fatty liver disease in guinea pigs
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Fibroblast growth factor 21 (FGF21) agonists have shown promising effects in preclinical models of non-alcoholic fatty liver disease (NAFLD) as well as in short-term clinical trials in patients with non-alcoholic steatohepatitis (NASH). Comparing drug formulation, dose, administration route and age, this exploratory study investigated effects of FGF21 on NAFLD-associated measures in a validated guinea pig model. In three separate studies, female guinea pigs received a high-fat diet prior to intervention with escalating doses of either recombinant native human FGF21 or a human FGF21 human recombinant analogue (FGF21/19 chimer) with an extended half-life. While no significant effects of native FGF21 on the investigated endpoints were observed, the long-acting FGF21/19 chimer significantly altered the levels of circulating lipids, increasing plasma concentrations of cholesterol (TC, LDLc and HDLc) in young guinea pigs (p < 0.01 for all three parameters). Relative liver weights were reduced in FGF21/19-treated young animals (p < 0.05) compared to mature animals, whereas FGF21/19 reduced body weights in both age groups (p < 0.001). The FGF21/19 chimer effects on dyslipidemia, body and liver weights particularly in young animals, support an age-associated difference in the FGF21 response. The limited effects of the native human FGF21 highlights potential species-associated differences of this compound.
Originalsprog | Engelsk |
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Tidsskrift | Basic & Clinical Pharmacology & Toxicology |
Vol/bind | 130 |
Udgave nummer | 3 |
Sider (fra-til) | 385-393 |
ISSN | 1742-7835 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
This research was funded in part by the Lifepharm Centre for In Vivo Pharmacology (grant #1001109652) and Novo Nordisk A/S (grant #1001110782). Joan Frandsen, Ricki Thanning and Lene Winther Takla are thanked for technical assistance. Novo Nordisk is thanked for supplying the native human FGF21 and the human FGF21 analogue as a generous gift.
Funding Information:
This research was funded in part by the Lifepharm Center for In Vivo Pharmacology (grant #1001109652) and Novo Nordisk A/S (grant #1001110782). The Lifepharm Center is funded through a collaborative research effort between Novo Nordisk and University of Copenhagen. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Publisher Copyright:
© 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd
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