LEP and overnutrition: Although the complete absence of leptin signaling is rarely found in humans, both undernutrition and overnutrition are able to produce significant changes in serum leptin concentrations, leptin sensitivity or in the development of neurocircuits that regulate energy homeostasis (Samuelsson et al., 2008; Chen et al., 2009; Vogt et al., 2014; Ralevski and Horvath, 2015).