Hypocretin (Orexin): What It Does and How It Links With Narcolepsy and Food Choices

Abstract Hypocretin is neuropeptide from lateral hypothalamus with two specific receptors. There is a wide anatomic distribution of the hypocretin-1 and hypocretin-2 receptors that suggests this neuropeptide exerts numerous functions. The hypocretin plays a physiological role as a central mediator of energy homeostasis and food intake and regulates neuroendocrine axes. Hypocretin also promotes excessive consumption of numerous substances considered rewarding, motivating the search for drugs, tasty foods, and other substances associated with the reward. Hypocretin deficiency characterizes narcolepsy type 1 with excessive daytime sleepiness and cataplexy. These patients have highest weight and after exposition to unrestricted access to snacks they eat almost four times more calories. In theory, patients with type 1 narcolepsy have less satiety with regard to food choices and snack ingestion. Studies are necessary to understand the mechanisms why hypocretin deficiency drives higher prevalence of obesity and other comorbities.