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。“衰老性厌食症”已经被描述，并且与减少的饥饿和奖励相关的进食相关，从而与减少的EI和最终的体重减轻相关。然而，奇怪的是，肥胖率在老年人中正在增加，并且在我们人口的这一快速增长的部分中，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“失调”的重要介质，但也有很好的证据表明，衰老不仅与食欲下降和进食动机有关，而且与准确调节EI的能力受损有关，从而适应能量不平衡。然而，这些发现的机制尚未得到很好的阐明，目前还不清楚负责肥胖发展和/或维持的机制是否受到年龄的影响。由于肥胖在老年人中的高患病率以及许多未回答的问题和争议，确定肥胖在该人群中的发展和/或持续性的机制以及这些机制是否与年轻人不同至关重要。此外，更好地了解老年人的EI调节也是至关重要的，如果我们要妥善管理这个不断增长的人口。这个试验项目的总体目标是开始检查年龄和肥胖相关的EI调节差异。具体来说，我们建议检查：1）神经元的反应，显着的视觉食物线索，并在冲动任务使用功能磁共振成像（fMRI）; 2）食欲相关的评级和肽; 3）进食相关的行为;和4）随意EI。这些评估将在老年肥胖（OOb）与老年正常体重（ONW）和老年肥胖（YOb）个体中进行比较。我们假设，与ONW相比，EI调节的措施将有利于OOb中EI的增加，证据如下：1）在编码奖励，动机和注意力的大脑区域中，对突出食物线索的神经元反应增加，以及对冲动任务的神经元反应增加; 2）食欲（↑饥饿，↓饱）和食欲相关肽（↓瘦素，↑生长激素释放肽，↓PYY/GLP-1）的测量差异; 3）进食评级增加。 相关行为;和4）增加随意EI。我们还假设，与YOb相比，EI调节的措施将有利于OOb的EI降低，证据如下：1）在编码奖励，动机和注意力的大脑区域中，对突出食物线索的神经元反应减少，以及对冲动任务的神经元反应减少; 2）食欲（↓饥饿，↑饱）和食欲相关肽（↑瘦素，↓ghrelin，↑PYY/GLP-1）的测量差异; 3）进食评分降低， 相关行为;和4）减少随意EI。超过35%的初级保健退伍军人肥胖，这一比例在老年退伍军人中可能更高。该项目产生的知识预计将指导VHA的治疗性减肥策略，并将推进GRECC关于老年人肥胖的后果和治疗的研究。

 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.