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 SH2B1 and metabolic disease.