Restricted Sleep: Modification of adiposity and adipose tissue composition

描述(由申请人提供)： 人们普遍推测，睡眠不足会导致身体肥胖增加，并导致肥胖相关疾病的风险因素的发展，例如与代谢综合征相关的疾病。实证研究很少。这项建议的目的是确定睡眠限制对生理和细胞通路的影响，这些通路是肥胖症和疾病推论变化的基础。中心假说指出，睡眠限制会导致脂肪代谢改变和脂肪组织表型的改变，特别是在炎症细胞的组成和生物活性多肽的分泌方面。脂肪分泌物的水平反过来又调节了一些与睡眠限制有关的迹象。初步数据支持验证这一假设的可行性，因为它提供了睡眠限制导致代谢失衡的证据，代谢失衡的特征是食物消耗量显著增加，但未能增加储存。这种代谢失调与轻微的全身性促炎状态和合成激素抑制有关，这些都是代谢综合征的共同征兆。在目标1下，将确定脂肪因子瘦素对睡眠限制引起的临床和病理体征的调节作用。这一目标的完成将通过睡眠缺失的研究显示瘦素抑制的临床意义。目标2下的实验旨在测试工作假设，即与其他器官相比，多个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。将测量脂肪组织的细胞组成和生物活性多肽和促炎分子的分泌。重塑脂肪组织的方式可能有利于疾病的进程，预计是由于睡眠限制导致的代谢失衡。研究设计包括不同睡眠剥夺量的计划比较，以及单一和多个周期的限制睡眠和反弹睡眠。分析方法包括生化分析、免疫分析和免疫组织化学分析。这项拟议的研究的意义在于，为睡眠限制对代谢途径和脂肪组织细胞的影响提供了切实的经验基础，可以有益地探索如何改变与睡眠不足相关的疾病的临床病程。

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.