GASTROINTESTINAL NUTRIENT SIGNALS CONTROLLING INGESTION

点击翻译按钮获取中文摘要

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.