Combined effect of high-fat diet and chronic sleep restriction on neurophysiological parameters of Wistar rats

Epidemiological studies have identified a functional bidirectional relationship between chronic sleep loss and the development of obesity. However, it remains unclear whether these factors amplify the damaging effects of each other on neurophysiological functions. This study aimed to investigate the combined effects of high-fat diet (HFD) and chronic sleep restriction (SR) on sleep characteristics and destructive changes in the locus coeruleus in male Wistar rats. Consumption of HFD for 10 weeks did not lead to changes in the organization of the wake-sleep cycle compared to control animals receiving standard dry chow (SD). However, during SR in a polyphasic regimen of 3 h of wakefulness and 1 h of sleep opportunity using a rocking platform for 5 days, the compensatory increase in slow-wave activity in response to lost sleep was less pronounced in rats on HFD during one-hour rest periods than in rats on SD. During the recovery period, a decrease in the amount of deep slow-wave sleep (SWS) in both groups was detected. However, after 14 days, this parameter reached the baseline level in the rats on SD, whereas this did not occur in the rats on HFD. It was found that SR was accompanied by neuronal death in the locus coeruleus, and the combination of HFD and SR augmented neurodegeneration. Thus, we demonstrated for the first time that chronic SR and HFD leads to pronounced disturbances in the homeostatic mechanisms of SWS regulation and subsequent deterioration of sleep quality, which could be a consequence of progressive dysfunction of the noradrenergic system of the locus coeruleus. The identification of the mutual negative influence of HFD and SR on sleep neurophysiology can be considered as a new risk factor for the development of metabolic diseases and other disorders of CNS functions.