Shortened sleep and food motivation: hypothalamic and striatal substrates

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DESCRIPTION (provided by applicant): The current 'epidemic' of obesity has been called one of the leading public health concerns worldwide; nevertheless, all of the factors predisposing individuals to obesity have not been identified. There is now provocative evidence from clinical studies that shortened sleep duration can lead to an obese phenotype, a particularly alarming finding given that that average sleep duration has decreased by 20% over the last 50 years. To explore the physiological mechanisms underlying the link between sleep restriction and obesity, we have developed a research plan designed to study the impact of shortened sleep duration on three major neurochemical systems involved in the central control of food intake: the mediobasal hypothalamic axis (involved in translating peripheral energy balance signals into behavior), the hypothalamic-pituitary-adrenal axis (which may be involved in stress-induced preferences for energy-dense foods), and striatal opioid and dopamine systems (which mediate higher-order processes related to food motivation). We also propose a detailed analysis of sleep restriction effects on key motivational and structural components of ingestive behavior, including feeding microstructure, flavor and macronutrient preference, and food reward. A unique feature of this proposal is the novel, innovative system that will be used to precisely restrict sleep and record several components of ingestive behavior directly within the apparatus itself. In addition, we will use a novel schedule of mild sleep restriction separated by periods of recovery, a method that may have greater face and construct validity than previous paradigms used in the literature. Relevance to public health: These studs have the potential to precisely identify the neural, endocrine, and behavioral mechanisms by which sleep curtailment may lead to increased risk for obesity. To date, these factors are poorly understood, and have been previously studied using sleep deprivation schedules that do not reflect the human condition. Understanding the mechanistic link between shortened sleep and obesity may lead to novel strategies/drug targets that could help curtail the obesity epidemic, and thereby hopefully reduce rates of cardiovascular disease and type 2 diabetes.