Restricted Sleep: Modification of adiposity and adipose tissue composition

限制睡眠：改变肥胖和脂肪组织成分

• 批准号: 7173597
• 负责人: CAROL A EVERSON
• 金额: $ 30.94万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-12 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7173597
• 关键词: adipose tissue; appetite; bioenergetics; biological signal transduction; body composition; cell population study; cellular pathology; fatty acids; hormone regulation /control mechanism; immunocytochemistry; immunologic assay /test; immunoregulation; inflammation; laboratory rat; leptin; lipid biosynthesis; lipid metabolism; metabolic syndrome; nutrient intake activity; nutrition related tag; obesity; overeating; pathologic process; peptides; sleep; sleep deprivation

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.

描述（由申请人提供）： 人们普遍猜测，限制睡眠会导致人体肥胖和与肥胖相关疾病的危险因素的发展，例如与代谢综合征相关的疾病。经验研究很少。该建议的目的是确定睡眠限制对生理和细胞途径的影响，这是肥胖和疾病推论的变化的基础。中心假设指出，睡眠限制会导致脂质代谢改变，并改变了脂肪组织表型，特别是关于其炎症细胞组成和生物活性肽的分泌。反过来，脂肪分泌的水平介导了与睡眠限制相关的一些迹象。初步数据通过提供证据表明睡眠限制导致代谢失衡的证据来支持检验该假设的可行性，其特征是食品消耗量明显增加，但无法增加存储。这种代谢失调与温和的全身性促炎状态和对合成代谢激素的抑制有关，这是由代谢综合征共享的体征。在AIM 1下，将确定脂肪因子瘦素限制睡眠限制引起的临床和病理体征的介导。该目标的完成将表明通过睡眠损失研究对瘦素抑制的临床意义。 AIM 2下的实验旨在测试以下假设：与其他器官相比，白色脂肪组织中加速脂肪生成的多个睡眠限制和睡眠恢复周期改变了脂肪酸的命运。 AIM 3的研究将确定脂肪组织表型的变化。将测量生物活性肽和脂肪组织促炎分子的细胞组成和分泌。预期以可能有利于疾病过程的方式重塑脂肪组织会导致睡眠限制引起的代谢失衡。研究设计由不同量的睡眠剥夺的计划比较，以及限制性睡眠和反弹睡眠的单一和多个周期。分析方法包括生化，免疫测定和免疫组织化学分析。拟议研究的意义是提供限制睡眠对代谢途径和脂肪组织细胞影响的有形的经验基础，可以对改变与睡眠不足相关的疾病的临床疾病临床过程进行有益的探索。