Stress, 'comfort' food, and obesity

压力、“舒适”食物和肥胖

基本信息

批准号：
10161773
负责人：
Yvonne Michelle Ulrich-Lai
金额：
$ 52.3万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-08 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10161773
关键词：
Acute Address Adult Amygdaloid structure Attenuated Axon Behavioral Biochemical Body Weight Brain region CNR1 gene Calories Chocolate Consumption Data Dependence Eating Electrophysiology (science)Emotional Endocannabinoids Energy Intake Exposure to Food Health Hyperglycemia Hyperphagia Impairment Individual Intake Knowledge Lead Lesion Marijuana Medial Mediating Mediator of activation protein Metabolic Molecular Moods Muscimol Neurons Neurosecretory Systems Obesity Palate Pharmacology Physiological Prefrontal Cortex Prosencephalon Rattus Recording of previous events Reporting Rewards Rodent Role Site Stress Sucrose Testing Time Tissues Viral Water Weight Work anandamide behavioral response biological adaptation to stress cannabinoid receptor cost designer receptors exclusively activated by designer drugs diet-induced obesity endocannabinoid signaling experimental study feeding food consumption high body mass index improved in vivo male neuromechanism novel obese person obesity prevention optogenetics prevent psychological stressor receptor binding response restraint stress stressor weight loss intervention western diet

项目摘要

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.

项目概要大多数人报告说，吃非常美味、热量高的“舒适”食物是一种缓解压力的方式事实上，有吃过美味食物史的人情绪有所改善，症状也减轻了。然而，舒适喂养需要付出巨大的代价。代谢健康，因为与压力有关的饮食者的体重指数较高，并且减肥更困难。有明确证据表明舒适喂养是许多人肥胖的主要原因，但我们对此知之甚少为什么会出现这种情况？该提案解决了我们知识中的两个关键差距。其次，它确定了舒适喂养缓解正常体重个体压力的机制。在饮食引起的肥胖（DIO）期间，这种压力缓解会受到损害，这对健康很重要。影响，因为它表明肥胖者不断增加消费的恶性循环我们建议以延长代谢健康为代价来维持有效的压力缓解。使用可口的“零食”范例来研究这些关系，其中大鼠每天两次获得少量可口的蔗糖溶液或水作为对照，给予大鼠有限的蔗糖摄入量（LSI）。范例减少食物摄入量以补偿蔗糖中的热量并维持正常身体体重，使我们能够分离出 LSI 减少正常体重压力反应的机制事实上，LSI 大鼠的神经内分泌（HPA 轴）、行为和代谢（能量此外，LSI 无法对 DIO 大鼠提供应激缓解作用。表明肥胖可能会增加缓解压力所需的可口食物的量。因此，范式提供了独特的机会来确定有效应力的潜在机制正常体重啮齿类动物的缓解情况、DIO 如何破坏这些机制以及 DIO 是否会升级蔗糖摄入量从而恢复有效的压力缓解，但代价是延长代谢健康。我们之前的工作表明前脑区域（BLA、mPFC）是 LSI 缓解压力的关键部位，尽管我们的新初步数据表明，调节这种压力钝化的神经回路机制尚不清楚。内源性大麻素（ECB；内源性大麻样分子）在该回路中发挥这种机制。例如，约束迅速增加压力会增加 LSI 大鼠的 BLA eCB（大麻素）含量，但不会增加水含量已知 BLA 中的 eCB 信号传导可以减弱全身性大麻素受体类型。 1 拮抗作用也阻碍了 LSI 压力的缓解，因此该提议提出了“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。实验确定了 PL-BLA 预测和前脑 eCB 信号对 LSI 压力缓解的贡献。实验还测试了 LSI 后 DIO 对前脑 eCB 信号传导的干扰程度，以及 DIO 期间增加蔗糖消耗恢复前脑 eCB 信号传导和应激减弱的能力。