Figure 6. Acute retinoid treatment results in inhibition of hepatic Fgf21 expression and RARα binding at the Fgf21 promoter is reduced with Fenretinide treatment.
C57BL/6 mice were on chow diet and ad libitum fed before a single injection of olive oil vehicle or 50 mg/kg RA or FEN for 2 hours, n = 8 for each group. (a) Hepatic gene expression of retinoid targets normalised to yWhaz. (b) Hepatic Fgf21 expression and (c) serum FGF21 levels. Significant differences were determined by one-way ANOVA followed by post-hoc tests or student’s t-test for Cyp26a1 FEN vs RA, Rarβ FEN vs vehicle, Fgf21 mRNA FEN vs vehicle and FGF21 serum FEN vs vehicle. Differences are marked *p < 0.05 vs vehicle or #p < 0.05 vs RA. (d) ChIP-qPCR of RARα binding at the hepatic Fgf21 RARE in mice injected with vehicle or 50 mg/kg FEN for 2 hours (n = 2 IP’s from 3 individual mice per group). IgG antibody was used to measure non-specific binding (IgG ab, n = 1). (e) ChIP-qPCR of RARα and polymerase (Pol) II binding at the hepatic Fgf21 and Cyp26a1 RAREs in mice fed HFD or HFD +FEN (FEN-HFD) for 20 weeks (n = 1 IP from 4 individual mice per group). IgG antibody was used to measure non-specific binding (IgG ab). Significant differences were determined by student’s t-test. Differences are marked *p < 0.05.