UPPER GI TRACT MEDIATION OF THE SATIETY EFFECTS OF FATS

上消化道对脂肪饱腹感的调节

• 批准号: 2405185
• 负责人: DANIELLE GREENBERG
• 金额: $ 18.45万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2405185
• 关键词: cholecystokinin; conditioning; dietary lipid; fasting; hunger; immunocytochemistry; laboratory rat; nutrition related tag; satiations; sham feeding; stomach emptying; vagotomy; vagus nerve

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.

描述（改编自申请人的摘要）：摄入高脂肪 饮食与严重的公共卫生问题有关，例如冠状动脉 心脏病、高血压、非胰岛素依赖型糖尿病等 癌症和肥胖。 许多报告表明，摄入量增加 膳食脂肪而不是总能量消耗会促进体重增加。 在 为了有效控制脂肪类食物的摄入，生理学 必须了解限制脂肪摄入的机制。 这个提议是为了 在 Sprague Dawley 大鼠和三种遗传性大鼠中鉴定这些机制 以脂肪摄入异常为特征的肥胖模型：Zucker fa/fa， Osborne Mendel 和 S 5B/PI 大鼠。 斯普拉格-道利提出了实验 确定对大鼠肠道的生理刺激程度 正常喂养时脂肪会发生什么刺激等影响 就餐量而言。 这将通过以下方式完成： (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进入肠道时 被摄入。 大多数实验采用假喂养程序来获得 完全控制肠道食物刺激；每一个现象 假喂养模型中确定的结果将在真实的测试中得到验证 通过以下方式喂养大鼠：（2）检查参与控制的机制 通过生理上适当的肠道脂肪输注来调整膳食量和 通过使用条件确定这些影响是否特定于饱腹感 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道饱足感； (4) 确定参与介导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大小。 该提案还旨在 (5) 确定口头和 肠道脂肪刺激控制膳食量。 （六）这些问题 也可在遗传性肥胖 Zucker、Osborne-Mendel 和 S 5B/pl 中进行探索 老鼠。 所有与摄入有关的实验治疗的效果将是 通过间隔摄入量和微观结构分析来测量 电子舔液计记录可以对每时每刻进行估计 积极（刺激）和消极（满意）反馈的相互作用 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 控制脂肪膳食期间脂肪摄入的机制。 研究与 遗传模型可能提供最近的分子生物学之间的联系 的进展，并为新的药物提供潜在的药理靶点 治疗肥胖症和贪食症中的暴饮暴食。