Cholinergic network modulation in disinhibited eating behavior

Cholinergic modulation of brain reward circuitry appears to play a crucial role in information processing about salience as a key biological mechanism in obesity. However, changes in acetylcholine transmission leading to abnormal eating behavior have not been demonstrated in vivo in human obesity. 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. This increase was accompanied by a shift from dorsal attention network activation in normal-weight controls to salience network activation in individuals with obesity indicating fundamental differences in sensory cue detection. These data should encourage further investigations into α4β2* nAChR in obesity, particularly with regard to treatment with nicotinic receptor agonists for weight loss targeting hedonic overeating.