Abstract <p>Among the negative consequences of chronic sleep deprivation,obesity and associated metabolic and neurobehavioral disorders areof significant importance. Chronic sleep deprivation leads to increased appetiteand a preference for high-calorie foods, which increases the riskof obesity. The cause-and-effect relationships between short sleepduration and the pathophysiology of obesity, as well as the consequencesof the combined effects of these factors on the body, remain poorlyunderstood. The aim of this study was to comparatively investigatethe effects of sleep restriction (SR) and high-fat diet (HFD)-inducedobesity, separately and in combination, on metabolic parametersand neurobehavioral functions in rats. We used a model of chronicSR (3 h of sleep deprivation on a rocking platform and 1 h of restfor 5 days) and HFD (8 weeks) in male Wistar rats. The control animalsreceived standard dry food. It was found that SR leads to body weightgain and an increase in adipose tissue mass, as well as impairedglucose tolerance. Moreover, the combination of SR and HFD expandsthe range of metabolic and hormonal disturbances, including reducedinsulin sensitivity, as indicated by elevated insulin levels andthe insulin resistance index. For the first time, we demonstratedthat the combination of SR and HFD also impairs neurocognitive performance,specifically working memory, as evidenced by reduced spontaneousalternation in the Y-maze test, whereas these parameters remainedunchanged in the SR-only or HFD-only groups. It was revealed thatworking memory impairment in the SR+HFD group may be associatedwith dysregulation of the dopaminergic system in the prefrontalcortex. The combined effects of SR and HFD can be considered asa significant risk factor for the development of metabolic disordersand cognitive deficits.</p>