Restricted Sleep: Modification of adiposity and adipose tissue composition

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DESCRIPTION (provided by applicant): It is widely speculated that restricted sleep leads to increased body adiposity and development of risk factors for obesity-related diseases, such as those associated with metabolic syndrome. Empirical studies are few. The objective of this proposal is to determine the effects of sleep restriction on physiological and cellular pathways that are the basis for changes in adiposity and disease corollaries. The central hypotheses states that sleep restriction results in altered lipid metabolism and changes to the adipose tissue phenotype, specifically with regard to its composition of inflammatory cells and secretion of bioactive peptides. The levels of the adipose secretions, in turn, mediate some of the signs associated with sleep restriction. Preliminary data support the feasibility of testing this hypothesis by providing evidence that sleep restriction leads to metabolic imbalance, characterized by marked increases in food consumption but failure to increase storage. This metabolic dysregulation is associated with a mild systemic proinflammatory state and suppression of anabolic hormones, which are signs shared by metabolic syndrome. Under Aim 1, mediation of clinical and pathological signs induced by sleep restriction by the adipokine leptin will be determined. Completion of this aim will show the clinical meaningfulness of leptin suppression by sleep loss research. Experiments under Aim 2 are designed to test the working hypothesis that multiple sleep restriction and sleep recovery cycles alter the fate of fatty acids by accelerated lipogenesis in white adipose tissue as compared to other organs. Studies under Aim 3 will identify changes in adipose tissue phenotype. The cellular composition and secretion of bioactive peptides and proinflammatory molecules from adipose tissue will be measured. Remodeled adipose tissue in ways that may favor disease processes would be expected to result from metabolic imbalance induced by sleep restriction. The research design is composed of planned comparisons of different amounts of sleep deprivation, and single and multiple cycles of restricted sleep and rebound sleep. The analytical methods include biochemical, immunoassay, and immunohistochemical analyses. The significance of the proposed research is the provision of a tangible, empirical basis of the effects of sleep restriction on metabolic pathways and adipose tissue cells, which can be gainfully explored for ways to alter the clinical course of diseases associated with insufficient sleep.