Defining mechanisms that regulate diet-induced wake impairments

定义调节饮食引起的觉醒障碍的机制

• 批准号: 9321028
• 负责人: Isaac Jeffrey Perron
• 金额: $ 1.14万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-12-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321028
• 关键词: Accidents; Acute; Adult; Affect; American; Animal Model; Area; Attention; Automobile Driving; Back; Behavior; Body Weight; Body Weight decreased; Brain region; Child; Chronic; Cognitive; Complement; Data; Diet; Disease; Drowsiness; Drowsy Driving; Fatty acid glycerol esters; Gene Activation; General Population; Genotype; Health; High Fat Diet; Homeostasis; Hormones; Hour; Hypothalamic structure; Impaired cognition; Impairment; Implant; Implanted Electrodes; Individual; Injectable; Intervention; Knock-out; Knowledge; Lead; Ligands; Mediating; Metabolic; Molecular; Motor Activity; Mus; Neural Pathways; Neurons; Neuropsychology; Non obese; Nuclear Receptors; Nutrient; Obese Mice; Obesity; Output; PPAR gamma; Peroxisome Proliferator-Activated Receptors; Productivity; Property; Protein Isoforms; Public Health; Quality of life; Randomized; Research; Risk; Role; Safety; Signal Transduction; Sleep; Sleep Fragmentations; Structure of nucleus infundibularis hypothalami; Testing; Time; United States; Up-Regulation; Viral; Wakefulness; Weight; alertness; behavioral impairment; behavioral study; cognitive function; dietary manipulation; energy balance; exercise regimen; feeding; good diet; improved; long chain fatty acid; median eminence; negative affect; novel; novel strategies; prevent; public health relevance; sleep abnormalities; vigilance

DESCRIPTION (provided by applicant): Obesity already affects over one-third of adults and nearly one-fifth of children in the United States. In addition to its association with various healh issues, obesity may negatively affect cognitive functioning, specifically vigilance and alertness. This in itself is another major public health concern, since these cognitive impairments heighten the risk for accidents and reduce productivity in the workforce. Further, obese individuals evidence both objective and subjective increases in sleepiness, which may underlie these cognitive effects. Increased sleepiness is prominent in animal models, as diet-induced obese (DIO) mice spend 2 hours more sleeping per day at the expense of wakefulness. These sleep abnormalities are reversed by normalization of body weight, but it is unclear whether initiation of weight loss (i.e. acute negative energy balance) is sufficient to restore this wake impairment; if true, beginning a healthy diet or exercise regimen may dramatically improve alertness and wakefulness in obese individuals. Therefore, this proposal will aim to define mechanisms and brain regions underlying wake impairments induced by diet/energy balance and/or obesity. First, energy balance will be bi- directionally modified by acute dietary manipulations in DIO mice. Second, we will examine the role of PPAR- gamma, which generally promotes positive energy balance, in mediating wake impairments in DIO mice. Our preliminary studies show that central PPARg inhibition in DIO mice prevents decreases in wakefulness. Thus, these studies will broaden and deepen our understanding of metabolic influences on sleep, which may provide novel strategies to improve alertness and attention in both obese and non-obese individuals.

描述（由申请人提供）：肥胖已经影响到美国超过三分之一的成年人和近五分之一的儿童。除了与各种健康问题相关外，肥胖还可能对认知功能产生负面影响，特别是警惕性和警觉性。这本身就是另一个重大的公共卫生问题，因为这些认知障碍增加了发生事故的风险，降低了劳动力的生产力。此外，肥胖个体在主观和客观上都表现出嗜睡的增加，这可能是这些认知效应的基础。增加的嗜睡在动物模型中是突出的，因为饮食诱导的肥胖（DIO）小鼠每天花费2小时以上的睡眠，以牺牲觉醒为代价。这些睡眠异常可以通过体重正常化来逆转，但目前还不清楚是否启动睡眠异常。 体重减轻（即急性负能量平衡）足以恢复这种清醒障碍;如果是真的，开始健康的饮食或锻炼方案可能会显着改善肥胖个体的警觉性和清醒性。因此，该提案旨在定义由饮食/能量平衡和/或肥胖引起的唤醒损伤的机制和脑区域。首先，DIO小鼠的能量平衡将通过急性饮食操作双向改变。其次，我们将研究过氧化物酶体增殖体激活受体-γ的作用，它通常促进正能量平衡，在介导清醒损伤DIO小鼠。我们的初步研究表明，在DIO小鼠中，中枢PPARg抑制可防止觉醒减少。因此，这些研究将拓宽和加深我们对代谢对睡眠影响的理解，这可能为改善肥胖和非肥胖个体的警觉性和注意力提供新的策略。