Restricted Sleep: Modification of adiposity and adipose tissue composition

描述（由申请人提供）： 人们普遍认为，睡眠不足会导致身体肥胖增加，并产生肥胖相关疾病的风险因素，如与代谢综合征相关的疾病。实证研究很少。该提案的目的是确定睡眠限制对生理和细胞途径的影响，这些途径是肥胖和疾病必然结果变化的基础。中心假设指出，睡眠限制导致脂质代谢改变和脂肪组织表型的变化，特别是关于其炎症细胞的组成和生物活性肽的分泌。反过来，脂肪分泌物的水平介导了一些与睡眠限制相关的体征。初步数据支持测试这一假设的可行性，提供的证据表明，睡眠限制导致代谢失衡，其特征是食物消费量显着增加，但未能增加存储。这种代谢失调与轻度全身促炎状态和合成代谢激素抑制相关，这是代谢综合征共有的体征。在目标1下，将确定脂肪因子瘦素对睡眠限制诱导的临床和病理学体征的介导。这一目标的实现将显示通过睡眠障碍研究来抑制瘦素的临床意义。目的2下的实验被设计为检验工作假设，即与其他器官相比，多次睡眠限制和睡眠恢复周期通过加速白色脂肪组织中的脂肪生成来改变脂肪酸的命运。目标3下的研究将确定脂肪组织表型的变化。将测量来自脂肪组织的生物活性肽和促炎分子的细胞组成和分泌。脂肪组织的重塑可能有利于疾病进程，这可能是由睡眠限制引起的代谢失衡引起的。研究设计包括有计划地比较不同程度的睡眠剥夺，以及单次和多次限制性睡眠和反弹性睡眠。分析方法包括生物化学、免疫测定和免疫组织化学分析。拟议研究的意义在于为睡眠限制对代谢途径和脂肪组织细胞的影响提供了有形的经验基础，可以有益地探索改变与睡眠不足相关疾病的临床过程的方法。

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.