NUTRITION AND OBESITY--PHYSIOLOGICAL MECHANISMS

关键是要确定和表征肥胖症的相关因素， 因此，预防或扭转与营养有关的负面影响的干预措施， 肥胖的健康后遗症可能会发展。要做到这一点，需要一个更好的 了解瘦-肥胖在决定肥胖的机制上的差异 人类食物摄入量。这些研究代表了第一个系统的 调查涉及监管的三个重要因素 肥胖和消瘦女性和男性的能量和常量营养素摄入量。这些 是：1）摄入食物的能量含量; 2）体积或重量 摄入的食物;和3）摄入的食物的宏量营养素组成。 我们的方法是使用严格的实验室程序来分离和 定义影响人体热量和常量营养素摄入的变量， 所提出的实验从逻辑上遵循先前的工作， 实验室已经对人类食物摄入量的决定因素进行了研究。 这些研究将利用新的食品技术， 允许开发可以口服或 灌胃，但在其感觉上没有可检测的差异 特性.使用胃内输注相同的食物， 口服提供了一种独特的工具， 认知控制（这是重要的线索，特别是肥胖 个体）从摄食后的能量生理控制和 大量营养素摄入量剂量-反应预加载范例提供了 最敏感的饱腹感指数，以及这项建议中的三项研究 具体来说，我们将测试假设， 与能量或体积检测相关的阈值升高或不存在 在肥胖个体中。我们还将测试的假设，热量为- 热量，脂肪提供的能量（与碳水化合物相比）将减少 在肥胖的人中得到满足。在所有研究中，我们将比较 肥胖和瘦个体的反应，以测试预测， 肥胖与以下因素有关：1）能量摄入调节受损; 2） 对脂肪提供的能量相对不敏感， 碳水化合物;和3）更依赖于orosensory/认知线索， 相比于进食后的影响。像这样的研究在 动物对人类的贡献产生了重要的见解， 口感觉、胃和胃后刺激在确定进食中的作用 行为，尽管尚未进行可比的系统研究 在人类中，拟议中的实验将提供关键的新信息， 能量含量，食物的体积或重量， 宏量营养素组成，以及口腔感觉和 能量和大量营养素调节中的摄食后因素 摄入这些信息对于奠定基础非常重要 更多的机械分析，以遵循和最终的发展， 预防或逆转肥胖相关疾病的干预措施。

It is critical to identify and characterize factors involved in obesity, so that interventions to prevent or reverse the nutrition-related negative health sequelae of obesity can be developed. To do so requires a better understanding of lean-obese differences in the mechanisms that determine human food intake. The proposed studies represent the first systematic investigation of three important factors involved in the regulation of energy and macronutrient intake in obese and lean females and males. These are: l) the energy content of ingested foods; 2) the volume or weight of ingested foods; and 3) the macronutrient composition of ingested foods. Our approach is to use rigorous laboratory-based procedures to isolate and define variables that affect human caloric and macronutrient intake, and the proposed experiments logically follow from previous work this laboratory has performed examining the determinants of human food intake. These studies will take advantage of new food technologies that have allowed the development of preload meals that can be consumed orally or infused intragastrically, yet do not differ detectably in their sensory properties. The use of intragastric infusions of the same foods that are consumed orally provides a unique tool for dissociating orosensory and cognitive controls (which are important cues particularly for obese individuals) from postingestive physiological controls of energy and macronutrient intake. A dose-response preloading paradigm provides the most sensitive index of satiety, and the three studies in this proposal reflect this design, Specifically, we will test the hypothesis that thresholds relating to energy or volume detection are elevated or absent in obese individuals. We will also test the hypothesis that calorie-for- calorie, energy provided by fat (as compared to carbohydrate) will be less satiating in obese individuals. In all studies we will be comparing the responses of obese and lean individuals to test the predictions that obesity is associated with: I) an impaired regulation of energy intake; 2) a relative insensitivity to energy provided by fat as compared to carbohydrate; and 3) a greater reliance on orosensory/cognitive cues as compared to postingestive influences. Studies like these performed in animals have generated important insights into the contributions of orosensory, gastric, and postgastric stimulation in determining eating behavior, although comparable systematic research has not been conducted in humans, The proposed experiments will provide crucial new information on the respective roles of energy content, the volume or weights of foods, macronutrient composition, and interactions between orosensory and postingestive factors in the regulation of energy and macronutrient intake. This information will be important in forming the foundation for more mechanistic analyses to follow and for the eventual development of interventions to prevent or reverse obesity-related illness.