UPPER GI TRACT MEDIATION OF THE SATIETY EFFECTS OF FATS

描述（改编自申请人摘要）：摄入高脂肪 饮食与严重的公共健康问题有关，如冠心病， 心脏病、高血压、非胰岛素依赖型糖尿病， 癌症和肥胖。 许多报告表明， 膳食脂肪，而不是总的能量消耗，促进体重增加。 在 为了有效地控制脂肪食物的摄入， 必须了解限制脂肪摄入的机制。 这项建议是为了 在Sprague道利大鼠和三种遗传学中鉴定这些机制， 以异常脂肪摄入为特征的肥胖模型：Zucker fa/fa， Osborne Mendel和S 5 B/PI大鼠。 实验在Sprague-Dawley提出 大鼠，以确定在何种程度上的肠道生理刺激 在正常喂养过程中发生的脂肪和什么样的影响，如刺激有 关于餐量 这将通过以下方式实现：（1）确定胃 排空率和进入的各种脂质部分的组成 当不同链长和饱和度的脂肪 被摄入体内 大多数实验采用假喂养程序， 完全控制肠道食物刺激;每一种现象 将在真实的试验中进行验证 通过以下方式喂养大鼠：（2）检查控制中涉及的机制 通过生理学上适当的肠脂肪输注， 确定这些影响是否是特定的饱腹感，通过使用条件 味觉厌恶范式;（3）确定迷走神经和CCK机制是否介导 由生理上适当的刺激引起的肠饱感;（4） 确定参与调节肠道控制的大脑区域， 通过使用c-Fos免疫组织化学和选择性脑损伤来确定膳食量。 该建议还试图（5）确定口头和口头的相互作用， 肠道脂肪刺激对膳食量的控制。 (6)这些问题将 在遗传性肥胖的Zucker、Osween-Mendel和S5 B/pl中也进行了探索 大鼠 所有涉及摄入的实验性治疗的效果将是 通过间隔进气口和微结构分析测量， 允许对每时每刻进行估计的电子粘度计记录 积极（刺激）和消极（满足）反馈的相互作用 在进餐期间摄入的食物和特定治疗的影响。 结果 这些研究将提供有关生物学的基本信息， 脂肪餐期间控制脂肪摄入的机制。 研究表明， 遗传模型可以提供最近的分子生物学之间的联系， 并为新的药物提供了潜在的药理学靶点。 治疗肥胖症和暴食症。

DESCRIPTION (adapted from applicant's abstract): Ingestion of high fat diets is associated with serious public health problems, such as coronary heart disease, hypertension, non-insulin dependent diabetes mellitus, some cancers, and obesity. Numerous reports suggest that elevated intake of dietary fat, rather than total energy consumption, promotes weight gain. In order to effectively control intake of fatty foods, the physiological mechanisms which limit fat intake must be understood. This proposal is to identify these mechanisms in Sprague Dawley rats, and in three genetic models of obesity characterized by abnormal fat intake: Zucker fa/fa, Osborne Mendel and S 5B/PI rats. Experiments are proposed in Sprague-Dawley rats to determine to what extent physiological stimulation of the intestine by fats occurs during normal feeding and what effect such as stimulation has on meal size. This will be accomplished by: (1) Determining the gastric emptying rates and the compositions of the various lipid moieties that enter the intestine when fats of different chain lengths and degrees of saturation are ingested. Most experiments employ the sham feeding procedure to gain complete control of intestinal food stimuli; Each of the phenomena determined in the sham feeding model will be validated in tests of real feeding rats by: (2) examining mechanisms that are involved in the control of meal size by physiologically appropriate intestinal fat infusions and determine if these effects are specific to satiety by use of conditioned taste aversion paradigms; (3) determine if vagal and CCK mechanisms mediate intestinal satiety elicited by physiologically appropriate stimuli; (4) determine the brain regions involved In mediating the intestinal control of meal size by use of c-Fos immuno-histochemistry and selective brain lesions. This proposal also seeks to (5) determine the interaction of oral and Intestinal fat stimuli in the control of meal size. (6) These issues will also be explored in genetically obese Zucker, Osborne-Mendel and S 5B/pl rats. The effects of all experimental treatments involved with ingestion will be measured by both interval intakes and by microstructural analysis of electronic lickometer records that permit 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 during fat meals. The studies with the genetic models may provide a link between recent molecular biological advances and also provide potential pharmacological targets for new treatments of obesity and of the binge eating that occurs in bulimia.