Role of Sex and Orexin in Sleep Disruption Induced Weight Gain

Abstract

Poor sleep time and quality associate with obesity in adults and women have a predisposition towards greater weight gain with sleep restriction. However, the mechanisms contributing to sex-specific sensitivity to weight gain following sleep loss remains unknown. Exposure to environmental noise is the only method of sleep disruption (SD) known to date that reduces sleep time and quality, stimulates weight gain and feeding and reduces distance traveled and energy expenditure (EE) (total and individual components) in male rats. The objective of this study was 1) validate the method of noise-induced sleep disruption in female rats, 2) determine mechanisms underlying the response to noise in male and female rats and 3) determine whether treatment with a sleep aid could block the effects of noise exposure independent of sex. Overall, findings from the study described in this dissertation demonstrate the following: 1) chronic exposure to noise increases weight gain and feeding and reduces total EE due to reductions in EE during spontaneous physical activity (SPA) and sleep without altering the length of the estrous cycle in female rats; 2) stress is not the primary mechanism underlying noise-induced weight gain in either male or female rats; and 3) Suvorexant, a Federal Drug Administration (FDA) approved dual orexin receptor antagonist for insomnia, significantly ameliorates noise-induced increases in time awake independent of sex but further exacerbates noise-induced increases in sleep fragmentation for males only. Collectively, these data have implications for future studies aimed to determine sex-specific sensitivity to weight gain following sleep loss. Furthermore, these data suggest that while Suvorexant may ameliorate reductions in sleep caused by noise equally in the sexes, the drug may have differential effects on the weight gain due to SD since Suvorexant further worsened sleep quality in males but not females.