The failure of the high-fat rats to show intake inhibition after i.c.v. glucose indicates that these responses were defective, a suggestion compatible with the knowledge of exacerbated activity of NPY neurons and decreased activity of POMC neurons in obesity.9, 44 The present finding of hyperleptinemia in the high-fat rats, indicative of leptin resistance, agrees with this hypothesis. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.