Fundamentals of FGF19 & FGF21 Action In Vitro and In Vivo (original) (raw)
Figure 3
Inhibition of FGF21 signaling also blocks FGF19 action in vitro.
Panel 1. In 3T3-L1/KLB fibroblasts co-treatment with the competitive agonist ΔN17 was able to block the induction of ERK phosphorylation caused not only by FGF21 but also by FGF19 (A). In our glucose uptake assay in 3T3-L1 adipocytes ΔN17 also suppressed the activity of both FGF19 (B) and FGF21 (C). Panel 2. To determine if the inhibition of FGF19/21 signaling we see in vitro translates to effects on metabolic parameters in vivo we examined fed and fasted glucose levels in ob/ob mice treated with FGF21, ΔN17 or a combination of both. In fed mice treatment with ΔN17 alone had no effect on serum glucose. FGF21 treatment reduced glucose levels significantly in the fed state, however, when the two treatments are combined the effect of FGF21 to reduce glucose is abolished (D). In fasted animals FGF21 again reduced glucose, an effect blocked by combination with ΔN17. Interestingly, we found that in fasted animals treatment with ΔN17 partially blocked the normal reduction in the serum glucose, suggesting ΔN17 may interfere in the regulation of glucose homeostasis (E).