a.
Specific Aims The obesity epidemic has highlighted the fact that many individuals have difficulty limiting their food intake tomaintain a healthy body weight on 'modern' or 'typical Western' diets. As science and the rest of societywrestle with the problems of explaining and controlling overconsumption of modern diets, it is surprising howlittle 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 orenhance 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 areused as signals to evaluate food and to limit consumption. In particular, since pre-absorptive and early postabsorptivesignals produced by nutrients constitute critical negative feedback that produces satiety and stopsintake of a meal, this proposal suggests a programmatic series of experiments designed to evaluate whatnutrient-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 todetermine 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' protocolis a hybrid procedure that combines elements of the chronic indwelling gastrointestinal catheter preparationand 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 intraintestinalinfusion of a novel nutrient and then is made ill by administration of an emetic or nausea-inducingdrug. In a subsequent test, the animal is given its first opportunity to taste and consume orally the nutrient thathad been paired with malaise. As we have reported (93), an animal, even in its first intake test, is able torecognize by mouth and reject the nutrient previously sampled in the intestines or stomach. In effect, this newprotocol offers the possibility of doing sensory 'psychophysics' on the nutrient sensitivities of the Gl tract.
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