Food Cues, Calories and Energy Regulation in Rats

描述（由申请人提供）：尽管我们在食物摄入和体重调节的神经、代谢和遗传控制方面的知识最近取得了进展，但肥胖的原因仍然难以捉摸，关于身体生理学或遗传学的变化如何导致当前肥胖流行的令人信服的解释尚未出现。本应用程序从一个新的理论公式来解决这个问题，该公式将摄入和体重的调节控制效率与巴甫洛夫条件反射的相对简单形式联系起来。在这个框架下，食用含很少或不含卡路里的甜味物质（如人造甜味剂）会降低甜味或感官线索预测卡路里的正常能力。这种预测关系减弱的结果是，含有卡路里的甜味食物不太能够唤起作为严格调节基础的代偿性生理反应。初步结果表明，暴露于这种非预测性关系可能损害能量调节的一种机制是通过破坏头期生理反应。研究建议确定头期反应和能量失调之间的关系，这些失调是由甜味和卡路里的非预测性经验产生的。此外，我们确定了这种经验变量的大小和影响如何与其他环境变量相互作用，包括维持饮食的组成和暴露于非预测性饮食的持续时间。最后，我们测试了是否暴露在其他饮食体验中，比如食用含有脂肪替代品的产品，这会降低味觉预测卡路里的能力，从而对体重调节产生类似的影响。在过去的25 - 30年里，美国食品环境的变化可能增加了人们对食物的感官特性不能预测其热量后果的饮食的接触。本提案中描述的工作考察了这种类型的破坏预测关系可能导致能量失调的具体机制；实验不仅可以确定能量失调发生的情况，还可以确定逆转这种损害的潜在方法。考虑到超重和肥胖持续增加的速度，确定这样的新方法变得越来越重要

DESCRIPTION (provided by applicant): Despite recent advances in our knowledge of the neural, metabolic and genetic controls of food intake and body weight regulation, the causes of obesity remain elusive and compelling explanations about how changes in body physiology or genetics might produce the current obesity epidemic have not been forthcoming. The present application approaches the problem from a novel theoretical formulation that links the efficiency of the regulatory control of intake and body weight to a relatively simple form of Pavlovian conditioning. Within this framework, consuming sweet-tasting substances (such as artificial sweeteners) which contain few or no calories has the effect of degrading the normal ability of sweet orosensory cues to predict calories. As a consequence of weakening this predictive relationship, sweet-tasting foods that contain calories become less able to evoke the compensatory physiological responses that underlie tight regulation. Preliminary results suggest that one mechanism by which exposure to such nonpredictive relationships may impair energy regulation is through a disruption of cephalic phase physiological responses. Studies are proposed to determine the relationship between cephalic phase responses and energy dysregulation produced by nonpredictive experience with sweet tastes and calories. In addition, we determine how the magnitude and impact of this experiential variable interacts with other environmental variables, including the composition of the maintenance diet and the duration of exposure to the nonpredictive diets. Finally, we test whether exposure to other dietary experiences, such as consumption of products manufactured with fat substitutes, which degrade the ability of tastes to predict calories produce similar effects on body weight regulation. Changes in the food environment in the U.S. over the past 25 - 30 years may have increased exposure to diets in which the sensory properties of a food are not predictive of its caloric consequences. The work described in the present proposal examines specific mechanisms by which this type of disruption predictive relationships could contribute to energy dysregulation; and the experiments may not only identify circumstances under which energy dysregulation occurs, but may also to identify potential approaches to reversing such impairment. Given the rapidity with which overweight and obesity continue to increase, identifying such novel approaches is becoming increasingly critical