Neural Mechanisms for Appetitive Responses to High Reward Foods

 描述（由申请人提供）：肥胖症越来越普遍，每年有超过280万人死于超重或肥胖。因此，确定防止体重增加和肥胖的因素对公共卫生极为重要。这项研究计划的总体目标是了解饮食行为的中央调节方式，可用于减少肥胖。这项特殊应用的目的是使用功能性磁共振成像（fMRI）来了解高奖励食物（包括摄入不同类型的糖）对人类食欲及其中枢调节的影响。我们先前发现，正常体重的成年人摄入葡萄糖和果糖这两种单糖后，神经内分泌和食欲会产生不同的反应。摄入果糖减少脑血流量（CBF），神经元活动的标志，在下丘脑（食欲区）小于摄入葡萄糖。果糖还刺激了两种潜在的饱腹感激素胰岛素和GLP-1的水平，低于葡萄糖，并且未能诱导葡萄糖摄入后观察到的饱腹感。这些初步研究为将果糖消费与暴饮暴食和肥胖联系起来的流行病学证据提供了机制性见解，并为本文提出的工作提供了强有力的理论基础。目前的建议将使用动脉自旋标记和fMRI血氧水平依赖（BOLD）技术的组合来检验以下假设：（1）与葡萄糖相比，果糖摄入将导致中枢食欲和奖赏通路中更大的食物线索反应性以及增加的进食行为;（2）蔗糖（50%葡萄糖和50%果糖）会产生类似于纯果糖而大于纯葡萄糖的大脑奖赏和激素反应;（3）摄入无热量甜味剂三氯半乳蔗糖将导致中枢食欲和奖赏区域的活动增加，并将导致对食物线索的食欲反应增强。这项研究意义重大，因为它将确定热量和非热量甜味剂对食欲和肥胖的神经生物学途径的影响。这些研究的结果将提供机械的见解和实用的信息，可用于帮助制定更有效的减肥和预防肥胖的饮食策略。

 DESCRIPTION (provided by applicant): Obesity is increasing prevalent, and over 2.8 million people die each year as a result of being overweight or obese. Consequently, identifying factors to prevent weight gain and obesity is extremely important to public health. The overall goal of this research program is to understand central regulation of eating behavior in ways that can be applied to reduce obesity. The objective of this particular application is to use functional magnetic resonance imaging (fMRI) to understand the effects of high reward foods, including the ingestion of different types of sugar, on appetite and its central regulation in humans. We previously found differential neuroendocrine and appetite responses to ingestion of two simple sugars, glucose and fructose, in normal- weight adults. The ingestion of fructose reduced cerebral blood flow (CBF), a marker of neuronal activity, in the hypothalamus (appetite region) less than ingestion of glucose. Fructose also stimulated levels of two potential satiety hormones, insulin and GLP-1, less than glucose and failed to induce the satiety that was observed after glucose ingestion. These preliminary studies provide mechanistic insights into epidemiological evidence linking fructose consumption to overeating and obesity and provide strong rationale for the work proposed here. The current proposal will use a combination of arterial spin labeling and fMRI-blood-oxygen- level dependent (BOLD) techniques to test the following hypotheses: (1) fructose compared to glucose ingestion will result in greater food-cue reactivity in central appetite and reward pathways and increased feeding behavior; (2) sucrose (50% glucose and 50% fructose) will produce brain reward and hormone responses that are similar to pure fructose and greater than pure glucose; (3) ingestion of the non-caloric sweetener, sucralose, will result in increased activity in central appetite and reward regions and will result in a heightened appetitive response to food cues. The proposed research is significant because it will determine the effects of caloric and non-caloric sweeteners on the neurobiological pathways underlying appetite and obesity. Findings from these studies will provide mechanistic insights and practical information that can be used to help develop more effective dietary strategies for weight loss and obesity prevention.