LEP and obesity due to melanocortin 4 receptor deficiency: Recently, it was shown that the long-term disruption of the genes encoding p110α and p110β, the catalytic subunits of PI3K, within the AgRP/NPY-neurons abrogates the leptin- and insulin-induced inhibition of AgRP/NPY-neurons and lead to the strengthening of orexigenic regulations, hyperphagia and obesity [40].