Appetite Regulation in Older-Aged Obese Individuals

 描述(由申请人提供)： 有很好的证据表明，能量摄入(EI)的调节随着年龄的增长而变化。“衰老厌食症”已被描述，并与减少饥饿和与奖励相关的进食有关，从而减少了EI，最终减轻了体重。然而，矛盾的是，老年人的肥胖率正在上升，在这一快速增长的人口部分中，肥胖和过度肥胖的问题变得特别普遍。虽然能量消耗和瘦体重的变化被认为是老年人体重调节或“调节失调”的重要因素，但也有很好的证据表明，衰老不仅与食欲和进食动机降低有关，还与准确调节EI从而适应能量失衡的能力受损有关。然而，这些发现的机制还没有被很好地阐明，也不清楚肥胖的形成和/或维持的机制是否受到年龄的影响。由于肥胖症在老年人中的高患病率以及许多悬而未决的问题和争议，确定肥胖在这一人群中发展和/或持续的机制以及这些机制是否不同于年轻人是至关重要的。此外，如果我们要适当地管理不断增长的人口，更好地了解老年人的EI监管也是至关重要的。这个试点项目的总体目标是开始检查与年龄和肥胖相关的EI调节的差异。具体地说，我们建议使用功能磁共振成像(FMRI)来检查：1)神经元对显著的视觉食物提示和在冲动任务中的反应；2)与食欲相关的评级和多肽；3)与进食相关的行为；以及4)即席EI。这些评估将在老年肥胖者(OOB)与老年正常体重(ONW)和年轻肥胖者(YOB)之间进行。我们假设，与OW相比，EI调节措施将有利于OOB患者EI的增加，这证明了：1)大脑编码奖励、动机和注意力的区域对显著食物提示以及冲动任务的神经元反应增加；2)食欲指标(↑饥饿、↓Satiet)和食欲相关肽(↓Leptin、↑Ghrelin、↓PYY/GLP-1)的差异；3)进食评级增加 相关行为；4)随意性EI增加。我们还假设，与YOB相比，EI调节措施将有利于OOB患者EI的下降，这一点得到了以下证明：1)大脑编码奖励、动机和注意力的区域对显著食物提示以及冲动任务的神经元反应减少；2)食欲指标(↓饥饿、↑Satiet)和食欲相关肽(↑Leptin、↓Ghrelin、↑PYY/GLP-1)的差异；3)进食评级下降 相关行为；4)随意性EI降低。在初级保健的退伍军人中，超过35%的人肥胖，这一比例在老年退伍军人中可能更高。该项目产生的知识有望指导VHA的治疗减肥战略，并将推动GRECC关于老年人肥胖后果和治疗的研究。

 DESCRIPTION (provided by applicant): There is good evidence that the regulation of energy intake (EI) changes with aging. The "anorexia of aging" has been described and is associated with reduced hunger and reward-related eating and thus with reduced EI and ultimately weight loss. Paradoxically, however, obesity rates are increasing in older individuals, and within this rapidly growing segment of our population, the problem of obesity and excess adiposity has become particularly widespread. While changes in energy expenditure and lean body mass are thought to be important mediators of body weight regulation or "dysregulation" in older individuals, there is also good evidence that aging is associated with not only reduced appetite and motivation to eat but also with impaired ability to accurately regulate EI and thus adapt to energy imbalance. The mechanisms, though, for these findings have not been well elucidated, and it is unclear whether the mechanisms responsible for the development and/or maintenance of obesity are impacted by age. Because of the high prevalence of obesity in older-aged individuals and the number of unanswered questions and controversies, it is critical to determine the mechanisms for the development and/or persistence of obesity in this population and whether the mechanisms are different from younger adults. Furthermore, better understanding EI regulation in older individuals is also critical if we are to properly manage this growing population. The overall goal of this pilot project are to begin to examine age- and obesity-related differences in the regulatio of EI. Specifically, we propose to examine: 1) the neuronal response to salient visual food cues and during an impulsivity task using functional magnetic resonance imaging (fMRI); 2) appetite-related ratings and peptides; 3) eating-related behaviors; and 4) ad libitum EI. These assessments will be performed in older obese (OOb) as compared to older normal weight (ONW) and younger-aged obese (YOb) individuals. We hypothesize that measures of EI regulation will favor increased EI in OOb as compared to ONW as evidenced by: 1) increased neuronal responses to salient food cues in brain regions encoding reward, motivation and attention, and to an impulsivity task; 2) differences in measures of appetite (↑hunger, ↓satiet) and appetite-related peptides (↓leptin, ↑ghrelin, ↓PYY/GLP-1); 3) increased ratings of eating related behaviors; and 4) increased ad libitum EI. We also hypothesize that measures of EI regulation will favor decreased EI in OOb as compared to YOb as evidenced by: 1) decreased neuronal responses to salient food cues in brain regions encoding reward, motivation and attention, and to an impulsivity task; 2) differences in measures of appetite (↓hunger, ↑satiet) and appetite-related peptides (↑leptin, ↓ghrelin, ↑PYY/GLP-1); 3) decreased ratings of eating related behaviors; and 4) decreased ad libitum EI. More than 35% of Veterans in primary care are obese and this percentage is likely even higher among older Veterans. The knowledge generated by this project is expected to guide therapeutic weight loss strategies in the VHA and will advance GRECC research on Consequences and Treatments of Obesity in Older Adults.