Z Gastroenterol 2019; 57(09): e242
DOI: 10.1055/s-0039-1695255
Leber und Galle
Tiermodelle für ACLF, Leberregeneration, Karzinogenese, Leberfribrose: Donnerstag, 03. Oktober 2019, 11:05 – 12:41, Studio Terrasse 2.1 A
Georg Thieme Verlag KG Stuttgart · New York

Fibroblast growth factor 21 (FGF21) response in alcohol induced “acute-on-chronic liver injury” (ACLI) model

G Christidis
1   Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Deutschland
,
E Karatayli
1   Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Deutschland
,
R Hall
1   Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Deutschland
,
S Weber
1   Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Deutschland
,
F Lammert
1   Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Deutschland
,
SC Karatayli
1   Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2019 (online)

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    Background and aims:

    The fibroblast growth factor (FGF) 21, which is known to be a stress-induced hormone in liver, has recently been shown to have a regulatory role in bile acid metabolism. In this study, we aim to investigate FGF21 response in acute on chronic liver injury (ACLI) model in Abcb4 -/- mice using ethanol challenge as the acute trigger.

    Method:

    Total RNA was extracted from liver tissue of 15 week-old wild type (WT) C57BL/6J and Abcb4 knock-out (KO) mice which were either fed with control diet (WT/Cont and KO/Cont groups) or liquid ethanol diet (5% v/v) followed by an acute ethanol binge (5 mg/kg) (WT/EtOH and KO/EtOH groups). Each group consisted of 16 mice (n = 64). Hepatic mRNA levels of Fgf21, Fgf15, Fgfr1, Fgfr4, Klb, Srebf1, Cyp7a1, Fxr, Shp, mTOR and Ppar-α were evaluated using 2-ΔΔCt method. Gapdh was used as an internal control. ELISA was performed for FGF15 and FGF21 using plasma samples. ANOVA followed by Bonferroni posthoc test was performed. P < 0.05 was considered as significant.

    Results:

    FGF21 response was significantly upregulated in WT/EtOH (p = 0.048) and KO/EtOH (p = 0.043) mice compared to their control diet fed counterparts, although no significant difference was found between genotypes. Elevation of FGF21 was also observed in plasma samples of WT/EtOH (p = 0.040) and KO/EtOH (p = 0.048) mice with similar statistical significance. Fgf15 expression was not observed in mice. FGF15 plasma levels showed no difference between groups. Expressions of Klb (p = 0.049) and Shp (p = 0.047) were significantly downregulated in KO/EtOH mice compared to the WT/Cont mice. Any significant difference was not observed for Srebf1, Fgfr1, Fgfr4, Fxr and mTOR expression levels between groups. Ethanol challenge resulted in about 2-fold increase in Ppar-α expression in both WT (p = 0.021) and Abcb4 -/- mice (p = 0.028). Expression level of Cyp7a1 was significantly downregulated in WT/EtOH (p = 0.009) and KO/EtOH (p = 0.008) mice when compared to WT controls.

    Conclusion:

    Upon ethanol challenge, bile acid metabolism might be regulated by upregulation of FGF21 resulting in an inhibition of CYP7A1 through a metabolic pathway independent of FGF15. Moreover, alcohol consumption might result in a Ppar-α dependent but mTOR independent regulation of FGF21 in this ACLI model.