In the present study, we use a conditional knockout system to specifically delete Ngn3 from the ventral forebrain, resulting in a depletion of Pomc expression in ARC neurons, a decrease in leptin sensitivity in the ARC and VMH nuclei, and an associated obesity due to hyperphagia and reduced energy expenditure. The gene discussed is NEUROG3; the disease is obesity due to melanocortin 4 receptor deficiency.