Indeed, the decreased baseline expression of hypothalamic leptin-dependent markers Pomc, Agrp, Npy and Mc4r, as well as their enhanced response to a fasting challenge, indicate an abnormal set-point and a larger dynamic range in the leptin-melanocortin system of EF females, which could be the cause of an abnormal energy balance and obesity. Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.