GASTROINTESTINAL NIUTRIENT SIGNALS CONTROLLING INGESTION

控制摄入的胃肠道营养信号

• 批准号: 7699724
• 负责人: TERRY L. POWLEY
• 金额: $ 24.22万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7699724
• 关键词: Address; Afferent Pathways; Animal Testing; Animals; Body Weight; Catheters; Chronic; Condition; Consumption; Cues; Diet; Digestion; Eating; Elements; Emetics; Epidemic; Feedback; Food; Gastrointestinal tract structure; Hybrids; Individual; Infusion procedures; Ingestion; Intake; Intestines; Learning; Malaise; Nature; Nausea; Nutrient; Obesity; Oral cavity; Organ; Pharmaceutical Preparations; Phase; Preparation; Procedures; Protocols documentation; Psychophysics; Reporting; Rest; Sampling; Satiation; Science; Sensory; Series; Signal Transduction; Site; Societies; Stimulus; Stomach; Taste Perception; Testing; Training; Visceral Afferents; Wrestling; design; detection of nutrient; gastrointestinal; novel; research study

a. Specific Aims The obesity epidemic has highlighted the fact that many individuals have difficulty limiting their food intake to maintain a healthy body weight on "modern" or "typical Western" diets. As science and the rest of society wrestle with the problems of explaining and controlling overconsumption of modern diets, it is surprising how little is known about the nutrient-sensing capacities of the gastrointestinal tract that can influence ingestion. Without such information, it is unlikely that it will be practical to design strategies that might maximize or enhance negative feedback loops and, ultimately, curtail meal-by-meal overconsumption. The overall long-term objective of the present proposal is a better understanding of how ingested nutrients are used as signals to evaluate food and to limit consumption. In particular, since pre-absorptive and early postabsorptive signals produced by nutrients constitute critical negative feedback that produces satiety and stops intake of a meal, this proposal suggests a programmatic series of experiments designed to evaluate what nutrient-generated signals can be detected by the gastrointestinal tract and/or organs of digestion. To address these issues, we have recently developed and used a test paradigm that makes it possible to determine what nutrient signals an animal is able to detect in the gut, or in the early post-absorptive phase (93). We have provisionally called this new protocol the intestinal taste aversion paradigm. This "ITA" protocol is a hybrid procedure that combines elements of the chronic indwelling gastrointestinal catheter preparation and the conditioned taste aversion paradigm (so that an animal will avoid a signal that it had detected while ill¿ ref. 31). Basically, in the training phase of the ITA paradigm, an animal receives an intragastric or intraintestinal infusion of a novel nutrient and then is made ill by administration of an emetic or nausea-inducing drug. In a subsequent test, the animal is given its first opportunity to taste and consume orally the nutrient that had been paired with malaise. As we have reported (93), an animal, even in its first intake test, is able to recognize by mouth and reject the nutrient previously sampled in the intestines or stomach. In effect, this new protocol offers the possibility of doing sensory "psychophysics" on the nutrient sensitivities of the Gl tract.

a.具体目标