LEP and obesity due to melanocortin 4 receptor deficiency: On the other hand, some evidence support the idea of a central resistance to leptin during obesity which is associated to peripheral hyperleptinaemia, probably more attributable to a reduction in leptin transport across the blood-brain-barrier (BBB) than to hypothalamic leptin insensitivity which would decrease the available amount of leptin at a hypothalamic level [142,322].