Human hypocretin-deficient narcolepsy - aberrant food choice due to impaired taste?

Authors demonstrate that patients with narcolepsy type 1 (N1) have more tendency of eat salty snacks after satiety than health volunteers. A few mechanisms to explain the weight gain have been discussed in narcolepsy. The hypocretin-1 deficiency can influence the olfactory system. The olfactory system should be modulated through hypocretin-1 via connections from the hypothalamic to other brain regions. Likewise, hypocretin-1 can be synthesized locally in our olfactory mucosa with possible private role modulating the olfactory. In experimental studies, different kinds of smell influence the preference for type of diet. Olfactory and taste sensations help control of appetite and regulate the quantity and quality of foods that will be chosen. N1 patients have lower levels of hypocretin-1 and consequent inferior olfactory threshold, less olfactory discrimination, and these findings improved after nasal hypocretin-1 administration. It is possible that the hyposmia influenced the quality and quantity of food by narcoleptic patients. We suggest that a complementary analysis of olfactory function should be done concomitant with food preferences to compare narcoleptic patients with and without hypocretin-1 deficiency.

Narcolepsy - Hypocretin-1 - Obesity - Olfaction

Recently, authors demonstrate that patients with narcolepsy type 1 have more tendency of eat salty snacks after satiety than health volunteers[1]. These findings are very promisor to help us to understand the frequent overweight of narcolepsy patients. A few mechanisms to explain the weight gain have been discussed in narcolepsy such as impairment of oxidative metabolism, hypothalamus dysfunction, and eating disorders[2].

The hypocretin-1 deficiency in narcolepsy type 1 patients drives daytime sleepiness, cataplexy, sleep palsy, sleep fragmentation, hallucinations, and autonomic changes[3]-[5]. However, hypocretin-1 can also influence the olfactory system for two different pathways. The hypocretin-1 projections can be detected in olfactory nuclei, brain cortex, tonsils, and nasal mucosa[6]. The olfactory system should be modulated through hypocretin-1 via connections from the hypothalamus to other brain regions. Likewise, hypocretin-1 can be synthesized locally in our olfactory mucosa with possible private role modulating the olfactory system[7],[8].

The olfaction is fundamental for regulating appetite. In experimental studies, different kinds of smell influence the preference for type of diet. Olfactory and taste sensations help control of appetite and regulate the quantity and quality of foods that will be chosen[9].

Patients with narcolepsy type 1 have lower levels of hypocretin-1 and consequent inferior olfactory threshold, less olfactory discrimination, and these findings improved after nasal hypocretin-1 administration[10]. In recent and interesting paper published by van Holst et al.[1], all patients with gustatory and hyposmia complains were excluded from original study. Thus, it is possible that the hyposmia influenced the quality and quantity of food sought by narcoleptic patients in this study, since olfactory conditions are directly related to changes in tasting. Indeed, a previous study in subjects without narcolepsy demonstrated higher occurrence of olfactory dysfunctions in obese patients[11]. We suggest that a complementary analysis of olfactory function should be done concomitant with food preferences to compare narcoleptic patients with and without hypocretin deficiency.

Conflict of Interests

The authors have no conflict of interests to declare.

• REFERENCES

• 1 van Holst RJ, van der Cruijsen L, van Mierlo P, Lammers GJ, Cools R, Overeem S, et al. Aberrant Food Choices after Satiation in Human Orexin-Deficient Narcolepsy Type 1. Sleep. 2016;39(11):1951-9. PMID: 27568806. PMCID: 5070749.
• 2 Kaufman DL, Ramesh V, McClatchey AI, Menkes JH, Tobin AJ. Detection of point mutations associated with genetic diseases by an exon scanning technique. Genomics. 1990;8(4):656-63. PMID: 2276738.
• 3 Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000;6(9):991-7. PMID: 10973318.
• 4 Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27(3):469-74. PMID: 11055430.
• 5 Fronczek R, Thijs RD. Autonomic alterations in narcolepsy-contrasting results in mice and men. Sleep. 2013;36(1):9-10. PMID: 23288964. PMCID: 3524547.
• 6 Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 1998;18(23):9996-10015. PMID: 9822755.
• 7 Stiasny-Kolster K, Clever SC, Möller JC, Oertel WH, Mayer G. Olfactory dysfunction in patients with narcolepsy with and without REM sleep behaviour disorder. Brain. 2007;130(Pt 2):442-9. PMID: 17235125.
• 8 Caillol M, Aioun J, Baly C, Persuy MA, Salesse R. Localization of orexins and their receptors in the rat olfactory system: possible modulation of olfactory perception by a neuropeptide synthetized centrally or locally. Brain Res. 2003;960(1-2):48-61. PMID: 12505657.
• 9 Stetter KR, McCann LI, Leafgren MA, Segar MT. Diet preference in rats (Rattus norvegicus) as a function of odor exposure, odor concentration, and conspecific presence. J Comp Psychol. 1995;109(4):384-9. PMID: 7497696.
• 10 Baier PC, Weinhold SL, Huth V, Gottwald B, Ferstl R, Hinze-Selch D. Olfactory dysfunction in patients with narcolepsy with cataplexy is restored by intranasal Orexin A (Hypocretin-1). Brain. 2008;131(Pt 10):2734-41. PMID: 18718966.
• 11 Richardson BE, Vander Woude EA, Sudan R, Thompson JS, Leopold DA. Altered olfactory acuity in the morbidly obese. Obesity Surg. 2004;14(7):967-9. PMID: 15329187.

Publication History

Received: 20 April 2017

Accepted: 02 May 2017

Article published online:
09 October 2023