Under normal conditions, it can cross the blood–brain barrier by facilitated diffusion and induce satiety and energy consumption by stimulating POMC and inhibiting neuropeptide Y. However, high concentrations induce a state of leptin resistance that favors the presence of obesity and other metabolic alterations by limiting the stimulation of extracellular signal-regulated kinases (ERK) 1 and 2, mitogen-activated protein kinase (MAPK), and other downstream factors [50]. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.