The loss of FTO leads to a misbalance of mBDNF to proBDNF in the hippocampus and a decreased downstream pathway activation.

(A) Representative western blot images showing the protein levels of proBDNF and mBDNF with actin as loading control on one gel. For better clarity, the distance between the bands was cut out. (B-C) Quantification of images indicated significant lower mBDNF amounts and equal proBDNF amounts in the hippocampus of Fto-/- mice, n = 6. (D) Representative western blot images of p-MAP2K1/2 with HPRT as loading control. (E) Quantification of images indicated a significant reduced MAPK pathway activity by revealing a decreased p-MAP2K1/2protein amount in the hippocampus of Fto-/- mice, n = 4. (F-G) Western blot analysis of the nonphosphorylated form of MAP2K1/2 showed no change in Fto-/- mice, n = 4. (H) Comparison of the nonphosphorylated and phosphorylated MAP2K1/2 amounts revealed a significant decreased of p-MAP2K1/2 to MAP2K1/2 ratio in the hippocampus of Fto-/- mice. (I) Relative quantification results from real-time PCR analysis for Bdnf mRNA transcripts revealed a slight downregulation in Fto-/- mice in the hippocampus, n = 8 Fto+/+ / 11 Fto+/+. Data are presented as mean ± S.E.M., unpaired t-test, *P < 0.05; ***P < 0.001.