The Effects of Enerty Imbalance on Food Intake Behaviors

描述(由申请者提供)：肥胖是美国和世界上一个严重且日益严重的公共健康问题。肥胖症日益流行的基础过程尚未明确定义，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。在目前的环境中，那些具有苗条遗传倾向的人可能会比那些有肥胖倾向的人更快、更准确地感觉到过量的能量摄入并对其做出反应。我们观察到，瘦(抗肥胖)的人很快就能感觉到能量平衡的变化，主观上对饥饿和饱腹感的衡量标准也发生了重大变化。这与肥胖减少(肥胖倾向)的人形成对比，他们似乎没有适当地感觉到能量摄入的短期变化。因此，摄食行为似乎有一种中枢调节，这种调节会因能量平衡的改变而改变，而且这种调节或多或少依赖于表型。是什么让我们对能量平衡的反应导致了行为的改变？大脑在调节能量平衡中的作用早已被认识到，并一直是一个密集的研究领域。关于下丘脑对食物摄取的调节以及与肥胖信号的相互作用，如瘦素，已经了解了很多。然而，很明显，食物的摄取是一个复杂得多的过程，特别是在人类中，心理社会因素在其中发挥着关键作用，进食过程可能受到奖励和习得行为的控制。我们的长期目标是更好地了解摄食行为的中央调节。此外，我们有兴趣了解与体重增加和肥胖风险较高的人相比，对体重增加和肥胖具有遗传抵抗力的瘦人对能量平衡变化(短期进食过多和进食不足)的适应情况。这项研究的中心假设是，食物摄取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觉输入和习得行为。具体地说，个体的动机状态受到能量平衡变化的控制，将导致参与处理和整合食物的激励价值和奖励的特定大脑区域的激活或抑制，而这些变化将与摄食行为相关。了解瘦人对短期不同能量平衡的行为和中枢神经元反应，将为在当前环境下防止体重增加的机制提供线索。这项拟议中的研究将考察摄入尤卡路里、喂养过多或喂养不足对以下方面的影响：1)局部脑神经活动，2)饥饿、饱腹感、享乐者、线索诱导的食物渴望和自发食物摄入量，以及3)被筛选为抵抗或容易体重增加和肥胖的男性和女性神经活动变化与行为指标之间的相关性。

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.