The Effects of Enerty Imbalance on Food Intake Behaviors

描述（由申请人提供）：肥胖是美国和世界上一个严重的和日益严重的公共卫生问题。肥胖症发病率增加的原因尚不清楚，但可能涉及环境因素与遗传易感个体体重调节系统之间的错误相互作用。那些在当前环境中有遗传倾向的人可能比那些有肥胖倾向的人更快更准确地感知和应对过量的能量摄入。我们已经观察到，瘦（抗肥胖）的人很快就能感觉到能量平衡的变化，饥饿和饱腹感的主观测量也发生了显著变化。这与减少肥胖（肥胖倾向）的个体形成对比，这些个体似乎不能适当地感知能量摄入的短期变化。因此，似乎有一个中央调节摄食行为，这是改变了能量平衡的变化，这种调节是或多或少敏感依赖于表型。我们对能量平衡的反应是什么导致了行为的改变？大脑在能量平衡调节中的作用早已被认识到，并且一直是深入研究的领域。关于下丘脑对食物摄入的调节以及与肥胖信号（如瘦素）的相互作用，人们已经了解了很多。然而，很明显，食物的摄入是一个复杂得多的过程，特别是在人类中，心理社会因素起着关键作用，并且进食过程可能受到奖励和学习行为的控制。我们的长期目标是更好地了解摄食行为的中枢调节。此外，我们感兴趣的是了解适应能量平衡的变化（短期过度和不足喂养）在薄的个人谁似乎是遗传抵抗体重增加和肥胖相比，个人在体重增加和肥胖的风险。这项研究的中心假设是，食物摄入的调节是一个复杂的过程，需要在背景能量平衡的背景下整合多种感官输入和学习行为。具体而言，个体的动机状态，如能量平衡的变化所操纵的，将导致激活或抑制特定的大脑区域，这些区域涉及食物的激励价值和奖励的处理和整合，并且这些变化神经元活动将与进食行为相关联。了解瘦个体对短期能量平衡变化的行为和中枢神经元反应，将为当前环境下防止体重增加的机制提供线索。拟议的研究将检查真热量摄入、过度喂养或喂养不足对以下方面的影响：1）局部脑神经元活动，2）饥饿、饱腹感、享乐主义、线索引发的食物渴望和自发食物摄入，以及3）筛选出抵抗或倾向于体重增加和肥胖的男性和女性中神经元活动变化与行为测量之间的相关性。

DESCRIPTION (provided by applicant): Obesity is a serious and growing public health problem in the United States and the world. The processes that underlie this increasing prevalence of obesity have not been clearly defined but likely involve faulty interactions between environmental factors with weight regulatory systems in genetically susceptible individuals. Those who are genetically predisposed to thinness in the current environment may be able to sense and respond to excess energy intake more rapidly and accurately than those predisposed to obesity. We have observed that thin (obese-resistant) individuals quickly sense changes in energy balance with significant changes in subjective measures of hunger and satiety. This is in contrast to reduced-obese (obese prone) individuals who do not appear to appropriately sense short-term changes in energy intake. It therefore appears that there is a central regulation of ingestive behaviors which is altered by changes in energy balance, and that this regulation is more or less sensitive dependent on the phenotype. What is it about our response to energy balance that leads to changes in behaviors? The role of the brain in the regulation of energy balance has long been recognized and has been an area of intensive research. A great deal has been learned about the hypothalamic regulation of food intake and interactions with adiposity signals such as leptin. It is clear, however, that the intake of food is a much more complex process, especially in humans in which psychosocial factors play a critical role and in which the process of eating is likely to be controlled by reward and learned behaviors. Our long term goal is to gain a better understanding of the central regulation of ingestive behavior. In addition, we are interested in understanding the adaptations to changes in energy balance (short-term over and under feeding) in thin individuals who appear to be genetically resistant to weight gain and obesity as compared to individuals at risk for weight gain and obesity. The central hypothesis of the proposed research is that the regulation of food intake is a complex process requiring the integration of multiple sensory inputs and learned behaviors in the context of background energy balance. Specifically, the motivational state of the individual as manipulated by changes in energy balance will result in the activation or inhibition of specific brain regions involved with the processing and integration of the incentive value and reward of food, and these changes neuronal activity will be associated with feeding behaviors. Understanding the behavioral and central neuronal responses of thin individuals to short periods of varying energy balance will provide clues to the mechanisms that may protect against weight gain in the current environment. The proposed studies will examine the effects of eucaloric intake, overfeeding, or underfeeding on: 1) regional cerebral neuronal activity, 2) hunger, satiety, hedonics, cue- elicited food craving, and spontaneous food intake, and 3) the correlation between changes in neuronal activity and behavioral measures in men and women screened to be either resistant or prone to weight gain and obesity.