UPPER GI TRACT MEDIATION OF THE SATIETY EFFECT OF FATS

摄入高脂肪饮食与严重的公共健康有关 问题，如冠心病，高血压，非胰岛素 依赖性糖尿病和肥胖症。 为了有效 控制脂肪食物的摄入，限制的生理机制 脂肪摄入量必须了解。 但目前， 脂肪在人类和动物中产生饱腹感的情况在很大程度上是未知的。 这 一项提案旨在确定这些机制在斯普拉格道利大鼠 在瘦的和遗传性肥胖的Zucker大鼠中， 以高脂肪摄入为特点。 实验提出：（1）， 确定短期吸收前饱腹的作用部位， 通过比较不同脂肪的饱腹感， 当脂肪刺激被限制为： (a)下肠，（B）上小肠或（c） 胃;（2）以确定是否迷走神经介导的组成部分， 脂肪的饱腹感效应取决于迷走神经的传入或传出纤维， Sprague-Dawley大鼠，并确定脂肪诱导的迷走神经通路是否 饱腹感在瘦的和遗传性肥胖的Zucker大鼠中正常运作;（3） 以确定迷走神经和CCK机制是否参与了 脂肪的预吸收饱腹效应是加性的;（4）确定是否 脂肪的吸收前饱腹效应存在性别差异 如果存在这种差异，那么确定性腺的作用， 在Sprague-Dawley和Zucker大鼠中观察到的差异中的激素; （5）肾上腺切除、糖皮质激素或 盐皮质激素替代和促肾上腺皮质激素释放因子 Zucker大鼠对脂肪的吸收前饱足效应。 的影响 将通过两次间隔摄入测量所有实验治疗的 并通过电子粘弹计记录的微观结构分析， 允许估计每时每刻的相互作用的积极 （刺激）和负面（饱腹）反馈效果的摄入食物 和特定的治疗方法。 这些研究的结果将提供以下基本信息： 控制脂肪摄入的生物机制 结果还可能 为新的暴食治疗提供潜在的药理学靶点 在暴食症和某些形式的肥胖症中发生的饮食，特别是 在女性中。

Ingestion of high fat diets is associated with serious public health problems, such as coronary heart disease, hypertension, non-insulin dependent diabetes mellitus, and obesity. In order to effectively control intake of fatty foods, the physiological mechanisms which limit fat intake must be understood. But at present, the mechanisms by which fats produce satiation in humans and animals are largely unknown. This proposal is designed to identify these mechanisms in Sprague Dawley rats and in lean and genetically obese Zucker rats, a rodent model of obesity characterized by high intake of fat. Experiments are proposed: (1) to determine the site of action for the short-term, preabsorptive satiating effect of fats by comparing the satiating potency of fats of different chain lengths and degrees of saturation when fat stimuli are limited to: (a) the lower intestine, (b) the upper small intestine or (c) the stomach; (2) to determine if the vagally mediated component of the satiety effect of fats depends upon afferent or efferent vagal fibers in Sprague-Dawley rats and determine if vagal pathways for fat-induced satiety operate normally in lean and genetically obese Zucker rats; (3) to determine if the vagal and CCK mechanisms involved in the preabsorptive satiating effect of fats are additive; (4) to determine if there are sex differences in the preabsorptive satiating effect of fats and if such differences exist, then determine the role of gonadal hormones in the observed differences in Sprague-Dawley and Zucker rats; and (5) to determine the effects of adrenalectomy, glucocorticoid or mineralocorticoid replacement, and corticotropin releasing factor in Zucker rats on the preabsorptive satiating effect of fats. The effects of all experimental treatments will be measured by both interval intakes and by microstructural analysis of electronic lickometer records that permits estimates of the moment-by-moment interaction of the positive (stimulating) and negative (satiating) feedback effects of ingested food and specific treatments during a meal. The results of these studies will provide fundamental information about the biological mechanisms that control fat intake. The results may also provide potential pharmacological targets for new treatments of the binge eating that occurs in bulimia and some forms of obesity, particularly among women.