Obesity also causes the development of leptin resistance centrally owing to the downregulation of the expression of leptin receptors and thus may disrupt the hypothalamic-pituitary-ovarian axis [64,65]. Even though the brain may develop resistance to leptin, the other tissues, like ovaries, continue to be leptin sensitive and thus are affected by the high levels of leptin in the circulation in obese individuals [50]. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.