In line with these results, SH2B1 directly binds, via its SH2 domain, to TrkB to enhance BDNF signaling in cell culture.[8g] Remarkably, ablation of Sh2b1 in PVHSH2B1 neurons abrogated the ability of PVH BDNF to protect against hyperphagia, obesity, and metabolic disorders. This evidence concerns the gene NTRK2 and obesity due to melanocortin 4 receptor deficiency.