Using simultaneous positron emission tomography and functional magnetic resonance imaging, we found an increased α4β2* nicotinic acetylcholine receptors (nAChR) availability in response to visually salient food cues in twenty individuals with obesity, particularly in those with high disinhibited eating behavior, whereas there was no change in sixteen volunteers served as normal weight control. Here, CHRNA4 is linked to obesity due to melanocortin 4 receptor deficiency.