There is a substantial body of evidence, derived from both preclinical and clinical studies, that gastrointestinal (GI) sensitivity to nutrients, particularly lipids, is diminished in obesity, as reflected by attenuated stimulation of appetite-regulatory hormones, including CCK and PYY, and disordered regulation of energy intake (18-21). This evidence concerns the gene PYY and obesity due to melanocortin 4 receptor deficiency.