Aberrant Food Choices after Satiation in Human Orexin-Deficient Narcolepsy Type 1

Besides influencing vigilance, orexin neurotransmission serves a variety of functions, including reward, motivation, and appetite regulation. As obesity is an important symptom in orexin-deficient narcolepsy, we explored the effects of satiety on food-related choices and spontaneous snack intake in patients with narcolepsy type 1 (n = 24) compared with healthy matched controls (n = 19). In additional analyses, we also included patients with idiopathic hypersomnia (n = 14) to assess sleepiness-related influences. Participants were first trained on a choice task to earn salty and sweet snacks. Next, one of the snack outcomes was devalued by having participants consume it until satiation (i.e., sensory-specific satiety). We then measured the selective reduction in choices for the devalued snack outcome. Finally, we assessed the number of calories that participants consumed spontaneously from ad libitum available snacks afterwards. After satiety, all participants reported reduced hunger and less wanting for the devalued snack. However, while controls and idiopathic hypersomnia patients chose the devalued snack less often in the choice task, patients with narcolepsy still chose the devalued snack as often as before satiety. Subsequently, narcolepsy patients spontaneously consumed almost 4 times more calories during ad libitum snack intake. We show that the manipulation of food-specific satiety has reduced effects on food choices and caloric intake in narcolepsy type 1 patients. These mechanisms may contribute to their obesity, and suggest an important functional role for orexin in human eating behavior. Study registered at Netherlands Trial Register. URL: www.trialregister.nl. Trial ID: NTR4508