Stress, 'comfort' food, and obesity

项目摘要 大多数人报告说，吃美味可口、热量高的“安慰”食物是一种缓解压力的手段 救灾事实上，有食用可口食物史的人改善了情绪， 对压力的生理和情绪反应。然而，舒适喂养的成本很高， 代谢健康，因为压力相关的进食者有更高的BMI，减肥更困难。尽管 有明确的证据表明，舒适喂养是许多人肥胖的主要原因，我们对此知之甚少。 为什么会这样这一建议填补了我们知识中的两个关键空白。首先，它决定了 舒适性喂养减轻正常体重个体压力的机制。其次，它确定了 这种压力缓解在饮食诱导的肥胖症（DIO）期间受损。这对健康很重要 影响，因为它表明了一个恶性循环，肥胖者不断增加他们的消费， 可口的食物，以保持有效的压力缓解在恶化代谢健康的代价。我们建议 研究这些关系使用可口的“零食”范式，其中大鼠每天两次获得一个 少量可口的蔗糖溶液或水作为对照。给予这种有限蔗糖摄入量（LSI）的大鼠 范例减少他们的食物摄入量，以补偿蔗糖中的热量，并保持正常的身体 体重，使我们能够隔离LSI减少正常体重的应激反应的机制 个体事实上，LSI大鼠的神经内分泌（HPA轴）、行为和代谢（能量） 动员）对压力挑战的反应。此外，LSI不能在DIO大鼠中提供应激钝化， 这表明肥胖可能会增加缓解压力所需的可口食物的量。的LSI 因此，这一范式提供了确定有效压力的机制的独特机会 减轻正常体重的啮齿动物，这些机制如何被DIO破坏，以及DIO是否升级 蔗糖摄入，从而以恶化代谢健康为代价恢复有效的压力缓解。此外，委员会认为， 我们先前的工作暗示前脑区域（BLA，mPFC）是LSI压力缓解的关键部位，尽管 介导这种压力钝化的神经回路机制尚不清楚。我们新的初步数据表明 内源性大麻素（eCB;内源性大麻样分子）作为这种机制在该回路中起作用。 例如，束缚应激会迅速增加LSI大鼠的BLA eCB（大麻素）含量，但不会增加水的含量。 对照，并且已知BLA中的eCB信号传导减弱应激反应。全身性大麻素受体型 1拮抗作用也阻止LSI应力缓解。因此，这一建议解决了可口的假设， 食物通过在压力期间通过eCB信号改变前脑回路功能来抑制压力反应。拟议 实验确定了PL-BLA投射和前脑eCB信号传导对LSI应激缓解的贡献。 实验还测试了LSI后DIO干扰前脑eCB信号传导的程度，以及 增加蔗糖消耗以恢复DIO期间前脑eCB信号传导和应激钝化的能力。

Project Summary The majority of people report eating highly palatable, calorically-dense ‘comfort’ foods as a means of stress relief. Indeed, individuals with a history of eating palatable foods have improved mood and reduced physiological and emotional responses to stress. However, comfort feeding comes at a significant cost to metabolic health, as stress-related eaters have higher BMIs and have more difficulty losing weight. Despite clear evidence that comfort feeding is a primary cause of obesity for many people, we know very little about why this is the case. This proposal addresses two critical gaps in our knowledge. First, it determines the mechanisms by which comfort feeding gives stress relief in normal weight individuals. Second, it identifies the extent that this stress relief is impaired during diet-induced obesity (DIO). This has important health implications, as it suggests a vicious cycle whereby obese individuals continually increase their consumption of palatable foods to maintain effective stress relief at the cost of worsening metabolic health. We propose to study these relationships using a palatable ‘snacking’ paradigm in which rats are given twice-daily access to a small amount of palatable sucrose solution, or water as a control. Rats given this limited sucrose intake (LSI) paradigm reduce their chow intake to compensate for the calories in the sucrose and maintain normal body weight, allowing us to isolate the mechanisms by which LSI reduces stress responses in normal weight individuals. Indeed, LSI rats have attenuated neuroendocrine (HPA axis), behavioral, and metabolic (energy mobilization) responses to a stress challenge. Moreover, LSI is unable to provide stress-blunting in DIO rats, suggesting that obesity may increase the amount of palatable food needed to obtain stress relief. The LSI paradigm therefore provides the unique opportunity to determine the mechanism underlying effective stress relief in normal weight rodents, how these mechanisms are disrupted by DIO, and whether DIO escalates sucrose intake thereby restoring effective stress relief at the cost of worsening metabolic health. Furthermore, our prior work implicates forebrain regions (BLA, mPFC) as key sites for LSI stress relief, though the neurocircuit mechanism that mediates this stress-blunting is not known. Our new preliminary data point to endocannabinoids (eCB; endogenous marijuana-like molecules) acting within this circuit as this mechanism. For instance, restraint stress rapidly increases BLA eCB (anandamide) content in LSI rats, but not water controls, and eCB signaling in the BLA is known to blunt stress responses. Systemic cannabinoid receptor type 1 antagonism also prevents LSI stress relief. This proposal therefore addresses the hypothesis that palatable foods curb stress responses by altering forebrain circuit function via eCB signaling during stress. The proposed experiments determine the contribution of PL-BLA projections and forebrain eCB-signaling to LSI stress relief. Experiments also test the extent to which DIO interferes with forebrain eCB signaling after LSI, as well as the ability of escalated sucrose consumption to recover forebrain eCB signaling and stress-blunting during DIO.