Body Weight and Metabolic Rate Changes in Narcolepsy: Current Knowledge and Future Directions

Narcolepsy is a known auto-immune disease that presents mainly in the teenage years with irresistible sleep attacks. Patients with narcolepsy, especially NT1, have been found to have a high prevalence of obesity and other metabolic derangements. This narrative review aimed to address the relationship between narcolepsy and changes in weight and metabolic rate, and discuss potential mechanisms for weight gain and metabolic changes and future research agendas on this topic. This article will provide a balanced, up-to-date critical review of the current literature, and delineate areas for future research, in order to understand the pathophysiological metabolic changes in narcolepsy. Articles using predefined keywords were searched for in PubMed and Google Scholar databases, with predefined inclusion and exclusion criteria. Compared to controls, patients with narcolepsy are more likely to be obese and have higher BMIs and waist circumferences. According to recent research, weight gain in narcolepsy patients may be higher during the disease’s outset. The precise mechanisms causing this weight gain remains unknown. The available information, albeit limited, does not support differences in basal or resting metabolic rates between patients with narcolepsy and controls, other than during the time of disease onset. The evidence supporting the role of orexin in weight gain in humans with narcolepsy is still controversial, in the literature. Furthermore, the available data did not show any appreciable alterations in the levels of CSF melanin-concentrating hormone, plasma and CSF leptin, or serum growth hormone, in relation to weight gain. Other mechanisms have been proposed, including a reduction in sympathetic tone, hormonal changes, changes in eating behavior and physical activity, and genetic predisposition. The association between increased body mass index and narcolepsy is well-recognized; however, the relationship between narcolepsy and other metabolic measures, such as body fat/muscle distribution and metabolic rate independent of BMI, is not well documented, and the available evidence is inconsistent. Future longitudinal studies with larger sample sizes are needed to assess BMR in patients with narcolepsy under a standard protocol at the outset of narcolepsy, with regular follow-up.