LEP and obesity due to melanocortin 4 receptor deficiency: Leptin enters the hypothalamus through fenestrated capillary and acts on LepR expressed on neurons in arcuate nucleus (ARC), dorsomedial hypothalamus (DMH), and ventromedial hypothalamus (VMH), enabling a feedback mechanism to maintain energy balance, thereby preventing obesity and metabolic disorders (Pandit et al., 2017).