The role of leptin in rodent and human sleep: A transdiagnostic approach with a particular focus on anorexia nervosa

This narrative review addressed to both clinicians and researchers aims to assess the role of hypoleptinemia in disordered sleep with a particular focus on patients with anorexia nervosa (AN). After introducing circadian rhythms and the regulation of circulating leptin, we summarize the literature on disordered sleep in patients with AN and in fasting subjects in general. We highlight novel single-case reports of substantially improved sleep within days after initiation of off-label metreleptin treatment. These beneficial effects are set in relationship to current knowledge of disordered sleep in animal models of an impaired leptin signaling. Specifically, both absolute and relative hypoleptinemia play a major role in animal models for insomnia, obstructive sleep apnea and obesity hypoventilation syndrome. We pinpoint future research required to complement our understanding of the role of leptin in sleep in patients with acute AN. Moreover, within the section clinical applications we speculate that human recombinant leptin may be useful for the treatment of treatment-resistant sleep-wake disorders, which are associated with (relative) hypoleptinemia. Overall, we stress the role of the hormone leptin in sleep.