LEP and obesity due to melanocortin 4 receptor deficiency: The WT mice that were switched to the HFD became leptin resistant (decreased pSTAT3 activation in the hypothalamus following leptin administration), but the leptin-supplemented Lepob mice, which became comparably fat, were not leptin resistant, suggesting that hyperleptinemia per se is required to induce the leptin resistance associated with obesity [22].