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: 2734062
• 负责人: JAMES P GIBBS
• 金额: $ 18.41万
• 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/2734062
• 关键词: cholecystokinin; conditioning; dietary lipid; fasting; hunger; immunocytochemistry; laboratory rat; nutrition related tag; obesity; 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(摘自申请者的摘要)：摄入高脂肪 饮食与严重的公共健康问题有关，例如冠状动脉 心脏病、高血压、非胰岛素依赖型糖尿病等 癌症和肥胖症。大量报告表明，摄入量增加 饮食中的脂肪，而不是总的能量消耗，会促进体重增加。在……里面 为了有效控制高脂肪食物的摄入量，生理性的 必须了解限制脂肪摄入的机制。这项建议是为了 在Spraogue Dawley大鼠身上以及在三种遗传基因中确定这些机制 以异常脂肪摄入为特征的肥胖模型：Zucker FA/FA， 奥斯本·孟德尔和S 5B/PI大鼠。实验计划在斯普拉格-道利进行 以确定大鼠肠道的生理刺激程度 脂肪是在正常喂养过程中发生的，刺激等有什么影响 关于一餐的大小。这将通过以下方式实现：(1)确定胃 排空率和进入体内的各种脂类成分 当脂肪的链长和饱和程度不同时，肠道 被摄取了。大多数实验都使用假喂食程序来获得 完全控制肠道食物刺激；每一种现象 在假饲养模型中确定的将在真实的测试中得到验证 喂饲大鼠：(2)检查参与控制的机制 通过生理上适当的肠道脂肪输注和 通过使用条件反射来确定这些影响是否是饱腹感特有的 味觉厌恶范式；(3)确定迷走神经和CCK机制是否起中介作用 生理上适宜的刺激引起的肠道饱足感；(4) 确定参与调节肠道控制的大脑区域 通过c-Fos免疫组织化学和选择性脑损害观察进食大小。 这项建议还试图(5)确定口头和口头的相互作用 肠道脂肪刺激在控制进餐大小。(6)这些问题将 在遗传性肥胖的扎克、奥斯本-孟德尔和S中也有发现5B/pl 老鼠。 所有与摄取有关的实验性治疗的效果将是 通过间隔摄入量和通过对 电子舔舌计记录允许逐个时刻的估计 正(刺激)和负(满足)反馈的相互作用 进食食物的影响和用餐期间的特定治疗。结果是 将提供有关生物的基本信息。 控制脂肪膳食中脂肪摄入量的机制。与美国大学的研究 遗传模型可能提供了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靶点 治疗肥胖症和暴饮暴食的方法。