It is thought that diet-induced obesity renders AgRP neurons resistant to the effects of leptin, based in part on the fact that exogenous leptin fails to reduce food intake or induce pSTAT3 in obese animals and does not inhibit AgRP neurons in ex vivo preparations from obese animals (Bates et al., 2003; Baver et al., 2014; Enriori et al., 2007; Knight et al., 2010; Wei et al., 2015). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.