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Pre-clinic model for sleep deprivation-induced obesity and hedonic intake due to noise exposure

$188,446R21FY2018NSNIH

University Of Arizona, Tucson AZ

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Abstract

Easy access to calories and poor sleep independently increase eating and weight gain. Sleep deprivation (SD) increases hedonic intake (eating palatable food for pleasure) and in humans environmental noise exposure causes SD, is detrimental to health and increases obesity risk. We have shown that noise (pre-recorded random city sounds) causes SD, hyperphagia and weight gain in male rats, which is novel and replicates human data. Yet this methodology must be established in female rodents as sex is a critical biological variable. The overall goal is to establish the method of SD by noise to induce obesity in female rodents, use the model to define the contribution of hedonic intake to SD-induced obesity and use these data to develop a non- invasive method to distinguish types of sleep (REM vs. non-REM). Aim 1 will use statistical learning methods and data mining to quantify REM and non-REM based on data collected from studies in this proposal (food intake, physical activity energy expenditure, EEG, EMG) and will establish SD by noise in females as a pre- clinical model for obesity due to SD. We will compare sleep disruption caused by noise exposure and the gentle handling technique; test whether sex moderates the effect of noise exposure on sleep, weight gain and food intake and whether Suvorexant (used clinically for insomnia) normalizes sleep in noise-exposed rats. Finally, data mining will be completed to address a critical need in the sleep field: to develop a high-throughput, non-invasive technique to distinguish REM vs. non-REM in rats. In humans, SD increases hedonic intake, which promotes obesity. Taste preference is highly variable and may modulate hedonic intake caused by SD. We show clear individual taste preferences for snacks using a cafeteria (CAF) diet protocol (i.e. rotating selection of palatable human snacks plus rodent chow ad lib). We also show SD by noise increases chocolate intake in sated rats with low initial preference for chocolate and maintains intake in rats with high preference. Thus, SD by noise may increase intake of palatable foods that would normally be avoided during adequate sleep. Aim 2 will test if the effects of SD by noise on hedonic intake and obesity are dependent upon sex and individual taste preferences in rats. We will test whether SD increases binge chocolate intake and intake of CAF diet snacks. The scientific premise is: SD in increases hedonic intake and promotes obesity in humans; environmental noise promotes SD in humans; and our pre-clinical model mirrors the human response to SD. We hypothesize that like male rats, SD due to noise will cause obesity in females and increase hedonic intake despite individual preference to in turn worsen obesity. The innovation lies in establishing a simple method of SD that replicates human SD-induced obesity; developing a non-surgical method to measure sleep types; and identifying how individual preferences affects hedonic intake and obesity caused by SD. Its significance lies in establishing a translational model of SD independent of sex to identify mechanisms underlying reward behavior and obesity propensity due to SD, with the ultimate goal of developing novel anti-obesity therapies.

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