Leptin is transported across the BBB by a saturable and unidirectional system (Hileman et al., 2002), and impairment of leptin transport across the BBB has been reported in obesity (Burguera et al., 2000), contributing to a leptin-resistant state (Caro et al., 1996). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.