Role of Hypocretin in Metabolic Effects of Sleep Loss

越来越多的动物和人类研究正在确定睡眠时间、体重调节和能量消耗之间的重要相互关系。本提案的目的是系统地评估动物模型中慢性部分睡眠限制的代谢和内分泌后果。具体来说，我们打算研究慢性部分睡眠限制对胃饥饿素、瘦素和下丘脑泌素之间相互作用的影响，以及对体重和能量消耗的调节。这些实验将在三种动物模型（大鼠，小鼠，猴子）中进行。我们将使用在大鼠和小鼠中建立的急性和慢性睡眠剥夺协议，并使其适应慢性睡眠剥夺

A growing number of animal and human studies are identifying important interrelationships between sleep amounts, body weight regulation and energy expenditure. The goal of this proposal is to systematically evaluate the metabolic and endocrine consequences of chronic partial sleep restriction in animal models. Specifically, we intend to examine the effects of chronic partial sleep restriction on the interaction between ghrelin, leptin and hypocretin and on the regulation of body weight and energy expenditure. These experiments will be conducted in three animal models (rat, mouse, monkey). We will use acute and chronic sleep deprivation protocols established in rats and mice and adapt them to conduct chronic sleep deprivation in metabolic recording chambers. We hypothesize that in these animal models chronic sleep deprivation will increase food intake more than energy expenditure, resulting in weight gain. Increased ghrelin and hypocretin, together with decreased leptin will be involved in mediating these changes. We will next test if increased hypocretin activity is involved in mediating some of these changes using knockout models. Our hypothesis is that increased hypocretin during sleep deprivation increases energy expenditure proportionally more than food intake. In hypocretin knockout mice, partial sleep deprivation will stimulate appetite through ghrelin/leptin-dependent, but hypocretin-independent pathway, without a counterbalanced increase in energy expenditure, resulting in obesity. These studies will be critical to extend our understanding of the association between chronic sleep loss, metabolism and body weight regulation.