LEP and obesity due to melanocortin 4 receptor deficiency: The non-LepR subset may play a role similar to the known leptin-sensitive AgRP neurons, which, once activated, cause massive obesity.18,25 Related to this, ob/ob or db/db mice, both with functional leptin deficiency, associated with increased neuron activity in the Arc,22 presumably due to loss of inhibitory action by leptin on LepR neurons, are severely obese.