LEPR and obesity due to melanocortin 4 receptor deficiency: Support for this strategy was provided by overexpression of a potent JAK2 activator SH2B adaptor protein 1 (SH2B1) in the hypothalamus (49), as well as overexpression of LepR activator growth factor receptor bound protein 10 (Grb10) in the AgRP/NPY and POMC/CART neurons (47), both of which protected against obesity in DIO mice