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 依赖型糖尿病和肥胖。为了有效地 控制高脂肪食物的摄入量，限制 必须了解脂肪摄入量。但目前，通过这些机制 脂肪能在人类和动物身上产生饱腹感，这在很大程度上是未知的。这 一项旨在在SD大鼠身上确定这些机制的提案 在瘦削和遗传性肥胖的Zucker大鼠中，肥胖的啮齿动物模型 以高脂肪摄入量为特征的。建议进行以下实验：(1) 确定短期、前期吸收饱足的作用部位 通过比较不同脂肪的饱和能力来影响脂肪的效果 当脂肪刺激限制在以下范围时，链长和饱和度： (A)下肠道；。(B)上小肠；或。(C) 胃；(2)确定迷走神经介导的成分是否 脂肪的饱腹感效应依赖于迷走神经的传入或传出 并确定迷走神经通路是否为脂肪诱导的 饱腹感在瘦削和遗传肥胖的扎克大鼠中正常运行；(3) 以确定迷走神经和CCK机制是否参与了 脂肪的吸收前期饱足作用是相加的；(4)确定 脂肪的吸收前饱足效应存在性别差异 如果存在这样的差异，那么就确定性腺的作用 荷尔蒙在SD大鼠和Zucker大鼠中的观察差异； 以及(5)确定肾上腺切除、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大鼠对脂肪的预吸收饱足作用。其影响 在所有实验治疗中，将通过两个间隔摄入量来衡量 通过对电子舔舌计记录的微观结构分析， 允许对正值的时刻交互作用进行估计 摄入食物的(刺激性)和负(满足性)反馈效应 并在用餐期间进行特定的治疗。 这些研究的结果将为以下方面提供基本信息 控制脂肪摄入的生物机制。结果也可能是 为狂欢的新疗法提供潜在的药理靶点 暴食症和某些形式的肥胖症的饮食，尤其是 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.