Interestingly, although leptin resistance in the LepRb-JAK/STAT/SOCS3 pathway in AgRP neurons occurs within a similar timeframe as we have examined here, the inhibition of AgRP neuronal electrical activity is not yet leptin resistant, suggesting that the timing of diet modification may be an important consideration for therapeutic approaches to obesity. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.