Mechanisms underlying weight gain during sleep disruption (SD) are unclear. Estrogen has protective effects on bodyweight and sleep in pre-menopausal women while weight gain associates with worse sleep in post-menopausal women. In female rats, SD increases weight gain and food intake while reducing energy expenditure and plasma estradiol (E2) levels. Here we determined if E2 deficiency and replacement mediated weight gain and hyperphagia during SD in female rats. We hypothesized that ovariectomy (OVX) would block SD-induced weight gain and hyperphagia while E2 replacement would reverse the effect of OVX during SD.


10-week-old female Sprague-Dawley rats (N = 30) underwent sham or OVX surgery. After post-surgical recovery, rats were randomized to sleep undisturbed or SD due to pre-recorded noise (8h/d during the light cycle when rats normally sleep), which has been validated to reduce sleep. After 14d, rats were implanted with 2 capsules (80uL, s.c.) of either sesame oil or E2 (360ug/mL). Rats continued to sleep undisturbed or had SD for 14d. Bodyweight and food intake were measured every 48 h throughout the study.


OVX significantly increased weight gain and food intake compared to sham (P < 0.05, all comparisons). SD failed to stimulate weight gain or food intake in females with OVX both before and after E2 or sesame oil capsule implantation. There was a significant interaction between the SD and E2 on weight gain and food intake.Among OVX rats treated with E2, SD increased weight gain compared to undisturbed sleep, but this difference was not statistically significant (P = 0.1, n = 5/capsule group). Food intake among E2-treated females with OVX was not significantly different.


In female rats, E2 is necessary for weight gain and hyperphagia previously observed during SD and the SD-induced weight gain may be mediated by the loss of the effect of E2 on energy expenditure.