GASTROINTESTINAL NUTRIENT SIGNALS CONTROLLING INGESTION

控制摄入的胃肠营养信号

• 批准号: 7877745
• 负责人: TERRY L. POWLEY
• 金额: $ 27.1万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7877745
• 关键词: Address; Afferent Pathways; Animal Testing; Animals; Behavioral; Biological; Body Weight; Catheters; Chronic; 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.

一个。具体目标 肥胖的流行强调了一个事实，即许多人很难将食物摄入量限制为 在“现代”或“典型的西方”饮食上保持健康体重。作为科学和其他社会 与解释和控制现代饮食过度消费的问题搏斗，令人惊讶的是如何 对于胃肠道的营养感应能力知之甚少，这会影响摄入。 没有这样的信息，设计可能最大化或 增强负反馈回路，并最终减少麦克服过度用餐。 本提案的总体长期目标是更好地理解摄入的营养 用作评估食物和限制消费的信号。特别是，由于吸收前和早期吸收术 营养产生的信号构成产生饱腹感和停止的关键负面反馈 该提案的摄入量建议是一系列编程实验，旨在评估什么 营养生成的信号可以通过消化的胃肠道和/或器官检测到。 为了解决这些问题，我们最近开发并使用了测试范式，使得 确定动物能够在肠道中检测到的营养素，或在吸收后早期发现 （93）。我们暂时将此新协议称为肠味厌恶范式。这个“ ITA”协议 是一种混合过程，结合了慢性留置胃肠道导管制备的元素 并有条件的味道厌恶范式（以便动物避免发出信号，表明它在病时发现了它。 参考。 31）。基本上，在ITA范式的训练阶段，动物接受了胃内或肠内 注入新型养分，然后通过催吐或恶心引起的给药不生病 药品。在随后的测试中，该动物获得了首次品尝和食用口服的营养素的机会 与不适配对。正如我们报道的（93），即使在第一次摄入测试中，动物也能够 通过嘴巴识别并拒绝先前在肠道或板条中采样的营养。实际上，这个新的 协议提供了对GL道的营养敏感性进行感官“心理物理学”的可能性。