Stress, 'comfort' food, and obesity

压力、“舒适”食物和肥胖

• 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
• 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

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.

项目摘要 大多数人报告饮食高度可口，热浓密的“舒适”食品作为压力的手段 宽慰。实际上，有饮食可口食品史的人有改善的情绪并减少了 对压力的生理和情感反应。但是，舒适的喂食付出了巨大的代价 代谢健康，由于与压力相关的食客的BMI较高，并且减肥更加困难。尽管 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 为什么是这种情况。该提案在我们的知识上解决了两个关键差距。首先，它决定了 舒适喂养的机制可以减轻正常体重个体的压力。其次，它标识了 在饮食引起的肥胖症（DIO）期间，这种缓解压力的缓解程度受到损害。这具有重要的健康 含义，这表明了一个恶性循环，肥胖的人不断增加他们的消费 可口的食物，以保持有效的压力缓解，以担心代谢健康。我们建议 使用可口的“零食”范式研究这些关系，其中每天两次获得大鼠 少量可口的蔗糖溶液或水作为对照。鉴于这种有限的蔗糖摄入量（LSI）的大鼠 范式减少了肉食的摄入量以补偿蔗糖中的卡路里并保持正常身体 重量，使我们能够隔离LSI减少正常重量应力反应的机制 实际上，LSI大鼠已经减弱了神经内分泌（HPA轴），行为和代谢（能量） 动员）对压力挑战的反应。此外，LSI无法在DIO大鼠中提供压力支重， 表明肥胖可能会增加减轻压力所需的可口食物的数量。 LSI 因此，范式提供了确定有效压力的机制的独特机会 缓解正常体重啮齿动物，这些机制如何被DIO破坏，以及DIO是否升级 蔗糖摄入量因此以担心代谢健康的成本恢复有效的压力缓解。此外， 我们先前的工作将前脑区域（BLA，MPFC）作为LSI压力缓解的关键站点，尽管 介导这种压力支重的神经电路机制尚不清楚。我们的新初步数据指向 内源性大麻素（欧洲央行；内源性大麻样分子）作用在该电路中作为该机制。 例如，克制压力迅速增加了LSI大鼠中的BLA ECB（anandamide）含量，但不是水 BLA中的对照和欧洲央行信号传导已知钝性应力反应。全身大麻素受体类型 1拮抗作用也可以防止LSI应力缓解。因此，该提议解决了可口的假设 食物曲线应力响应通过在压力期间通过欧洲央行信号改变前脑电路功能来反应。提议 实验决定了PL-BLA项目的贡献和前脑ECB信号对LSI应力缓解的贡献。 实验还测试了DIO在LSI后干扰前脑欧洲央行信号的程度，以及 在DIO期间，逐渐消耗的蔗糖消耗能够恢复前脑欧洲央行信号传导和应力支重的能力。