Altered sleep regulation in leptin-deficient mice

Abstract

Recent epidemiological, clinical, and experimental studies have demonstrated important links between sleep duration and architecture, circadian rhythms, and metabolism, although the genetic pathways that interconnect these processes are not well understood. Leptin is a circulating hormone and major adiposity signal involved in long-term energy homeostasis. In this study, we tested the hypothesis that leptin deficiency leads to impairments in sleep-wake regulation. Male ob/ob mice, a genetic model of leptin deficiency, had significantly disrupted sleep architecture with an elevated number of arousals from sleep [wild-type (WT) mice, 108.2 ± 7.2 vs. ob/ob mice, 148.4 ± 4.5, P < 0.001] and increased stage shifts (WT, 519.1 ± 25.2 vs. ob/ob, 748.0 ± 38.8, P < 0.001) compared with WT mice. Ob/ob mice also had more frequent, but shorter-lasting sleep bouts compared with WT mice, indicating impaired sleep consolidation. Interestingly, ob/ob mice showed changes in sleep time, with increased amounts of 24-h non-rapid eye movement (NREM) sleep (WT, 601.5 ± 10.8 vs. ob/ob, 669.2 ± 13.4 min, P < 0.001). Ob/ob mice had overall lower body temperature (WT, 35.1 ± 0.2 vs. ob/ob, 33.4 ± 0.2°C, P < 0.001) and locomotor activity counts (WT, 25125 ± 2137 vs. ob/ob, 5219 ± 1759, P < 0.001). Ob/ob mice displayed an attenuated diurnal rhythm of sleep-wake stages, NREM delta power, and locomotor activity. Following sleep deprivation, ob/ob mice had smaller amounts of NREM and REM recovery sleep, both in terms of the magnitude and the duration of the recovery response. In combination, these results indicate that leptin deficiency disrupts the regulation of sleep architecture and diurnal rhythmicity.