Revathi Pillai Abstracts

Revathi Pillai Abstracts

Revathi Pillai

M.S. Candidate
Physiological Sciences

ObesityWeek

Las Vegas, NV
November 4-7, 2019

Background: 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.

Methods: 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.
 

Results: 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.
 

Conclusion: 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.

Abstract for Lay Audience

The human population struggles with the epidemic of obesity and poor sleep, but women are more affected by both conditions compared to men. It remains unclear why women gain weight during sleep disruption, but the weight gain may be related to the steroid hormone, 17-beta-estradiol, which is predominantly found in females and begins to decline at the onset of menopause. This hormone has a protective effect on body weight by preventing weight gain. In female rats, surgically removing the ovaries with a procedure called an ovariectomy decreases estradiol levels and increases both food intake and body weight gain. Similarly, sleep disruption increases food intake and body weight gain and decreases plasma estradiol levels and energy expenditure. Thus, it’s plausible that restoring estradiol levels after an ovariectomy may reduce the weight gain and excessive eating during sleep disruption. Thus, we hypothesized that an ovariectomy would stop the sleep-disruption induced weight gain and excessive eating, and the estradiol replacement would reverse the effect of the ovariectomy during sleep disruption. To test this hypothesis, female rats either had their ovaries removed via an ovariectomy or had a sham surgery (same incision but ovaries remained). After a recovery period, the rats either slept undisturbed (control) or were exposed to pre-recorded noise (8h/d), which caused sleep disruption. After this treatment period for 14 days, the rats were implanted with either 2 capsules that slowly released estradiol or sesame oil (control). Rats continued to sleep undisturbed or had sleep disruption for an additional 14 days. Bodyweight and food intake were measured every 48h throughout the duration of the study. We found that the ovariectomy increased weight gain and food intake. Sleep disruption did not further promote weight gain or food intake in the ovariectomized rats before estradiol capsule implantation. Overall, estradiol replacement reduced weight gain but not food intake in the ovariectomized rats. Also, Sleep disrupted rats the received estradiol replacement gained more weight than those that slept undisturbed. Thus, we conclude that estradiol is involved in the controlling the weight gain that occurs during sleep disruption in female rats. One mechanism that potentially controls the estradiol-related change in weight gain may be energy expenditure levels since food intake was unaffected by estradiol replacement in the ovariectomized female rats. If we can identify the role that estradiol and sleep disruption plays in an animal model, in the long-run, we can better understand the mechanisms that contribute to greater weight gain and worse sleep among women.