Gastrointestinal Nutrient Signals Controlling Ingestion

肥胖症的流行突出了这样一个事实，即许多人难以限制他们的食物摄入量， 以“现代”或“典型的西方”饮食保持健康的体重。作为科学和社会的其他部分 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， 对胃肠道的营养感应能力知之甚少，这种能力会影响摄取。 如果没有这些信息，就不太可能设计出能够最大限度地提高或 加强负反馈循环，最终减少每餐的过度消费。 目前建议的总体长期目标是更好地了解营养素的摄入情况， 用作评估食物和限制消费的信号。特别是，由于吸收前和吸收后初期 营养素产生的信号构成了产生饱腹感和停止的关键负反馈 这一提议建议进行一系列有计划的实验，旨在评估 可以通过胃肠道和/或消化器官检测营养物产生的信号。 为了解决这些问题，我们最近开发并使用了一种测试范例， 确定动物能够在肠道或吸收后早期检测到哪些营养信号 （93）。我们暂时将这一新方案称为肠道味觉厌恶范式。这个“ITA”协议 是一种混合程序，结合了长期留置胃肠道导管准备的要素， 和条件性味觉厌恶范式（这样动物就会避免它在生病时检测到的信号）。 参考文献31）。基本上，在ITA范例的训练阶段，动物接受胃内或肠内刺激。 输注一种新的营养素，然后通过施用催吐剂或恶心诱导剂而生病 药在随后的测试中，动物第一次有机会品尝和口服营养素， 都伴随着不适正如我们所报道的（93），动物，即使在第一次摄入试验中，也能够 通过口腔识别并拒绝先前在肠道或胃中采样的营养素。实际上，这个新 方案提供了对胃肠道的营养敏感性进行感觉“心理物理学”的可能性。

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.