LEP and obesity due to melanocortin 4 receptor deficiency: In further support of such a model of over-reactivity of the leptin-LepRb system in causing obesity, it has been reported that leptin itself (hyperleptinemia) is required for the development of neuronal leptin resistance (impaired STAT3 phosphorylation in response to exogenous leptin) in the ARC of HFD mice [47].