UPPER GI TRACT MEDIATION OF THE SATIETY EFFECTS OF FATS

上消化道对脂肪饱腹感的调节

基本信息

批准号：
2905356
负责人：
JAMES P GIBBS
金额：
$ 18.96万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-04-01 至 2001-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2905356
关键词：
cholecystokinin conditioning dietary lipid fasting hunger immunocytochemistry laboratory rat nutrition related tag obesity satiations sham feeding stomach emptying vagotomy vagus nerve

项目摘要

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，非胰岛素依赖性糖尿病，有些癌症和肥胖。许多报告表明摄入量的升高饮食脂肪而不是总能量消耗，可以促进体重增加。在为了有效控制脂肪食品的摄入量，生理必须理解限制脂肪摄入的机制。该建议是在Sprague Dawley大鼠和三个遗传中识别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 5B/PI大鼠。实验是在Sprague-Dawley中提出的大鼠确定肠的生理刺激程度通过脂肪在正常喂养期间发生，刺激等效果关于餐大小。这将通过：（1）确定胃排空率和输入各种脂质部分的组成当不同链长度和饱和度的脂肪时的肠道被摄取。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；每个现象在假喂养模型中确定的真实测试将验证喂养大鼠：（2）检查对照中涉及的机制通过生理上适当的肠道脂肪输注和通过使用条件确定这些效果是否特定于饱腹感品尝厌恶范式；（3）确定迷走神经和CCK机制是否介导生理上适当的刺激引起的肠饱腹感；（4）确定介导的大脑区域通过使用C-FOS免疫 - 归化学和选择性脑部病变的饮食大小。该提案还试图（5）确定口头的相互作用和饮食大小的控制中的肠脂肪刺激。（6）这些问题将也可以在基因肥胖的扎克，奥斯本 - 孟德尔和S 5B/PL中探索老鼠。摄入涉及的所有实验治疗的影响将是通过间隔摄入量和微结构分析来衡量允许逐步估算的电子滤光度记录正面（刺激）和负反馈的相互作用进餐期间摄取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饮食脂肪摄入的机制。与遗传模型可以提供最近分子生物学之间的联系进步，还为新的药理目标提供了潜在的药理目标肥胖和贪食症发生的暴饮暴食治疗。