Effect of fat loss on functional and cardiovascular benefits of aerobic exercise

描述(申请人提供)：衰老与有氧能力、运动耐力和机能耐力的下降有关，这些都会导致身体残疾。到目前为止，定期锻炼是唯一能持续改善有氧功能，或许还能延缓残疾发生的疗法。然而，一些数据表明，运动改善有氧功能的最大效果因肥胖而变得迟钝。此外，我们的初步数据显示，伴随的脂肪减少对运动诱导的有氧功能改善具有潜在的剂量-反应益处。因此，在肥胖老年人中，结合运动干预和卡路里限制导致脂肪减少可能比单独锻炼更有效地改善有氧功能，而肥胖老年人是残疾的高危人群。这项研究是一项为期5个月、为期3个月的随机临床试验，对象为180名老年人(65-79岁)、肥胖(BMI=30-34.9公斤/平方米)、久坐不动的男性和女性，旨在确定脂肪减少量(通过控制喂养不足实现)是否影响遵循当前建议的标准化运动训练刺激对有氧功能(最大有氧能力和耐力)改善的幅度。参与者将被随机分为运动训练干预组(中等强度跑步机步行，4d/wk)，单独运动(仅限EX)，中等热量限制运动(-250千卡/d减脂)，为低脂肪减肥设计的运动(低CR；~3.4公斤脂肪损失)，或高热量限制运动(-750千卡/d赤字)，为高脂肪损失(EX High CR；~10.2 kg脂肪损失)设计。具体目的是确定在标准化有氧运动训练干预中增加中等和高强度热量限制对以下方面的影响：1)最大有氧能力和步行耐力(6分钟步行距离)；2)心血管疾病风险因素(炎症标记物、血脂、血压、糖耐量和内皮功能)；以及3)肌肉间、腹部内脏和心包脂肪体积。我们还将确定有氧功能和心血管危险因素的改善是否与总脂肪和局部脂肪减少的程度有关。如果我们的假设得到证实，这项研究将从一项随机对照试验中提供第一个前瞻性和确凿的证据，即减少脂肪质量会增加运动诱导的有氧功能的改善。这些发现将提供有说服力的证据，表明在老年肥胖成年人的运动干预中增加卡路里限制可能比单独锻炼更有效地改善有氧功能，并可能改变传统上不愿建议老年人在锻炼计划中限制卡路里以最大化运动努力的传统。此外，通过评估干预前后内脏器官、骨骼肌和心肌周围的脂肪积累，我们还将能够确定这些局部储存库中脂肪减少对运动导致的功能和心血管危险因素结果改善的程度的贡献。与公共健康相关：这项研究将确定，在运动训练计划中减掉更多脂肪的老年肥胖男性和女性，是否会因为运动训练而在健康和耐力方面比那些没有减掉任何脂肪或脂肪很少的人有更大的改善。这一知识可能会导致更强有力的临床建议，将减肥纳入其中，以造福于锻炼的肥胖老年人。研究结果还将提供有关脂肪减少的位置是否对改善健康和心血管疾病风险很重要的信息。

DESCRIPTION (provided by applicant): Aging is associated with declines in aerobic capacity, exercise tolerance, and functional endurance that lead to physical disability. To date, regular exercise is the only therapy to consistently improve aerobic function, and perhaps delay the onset of disability. However, some data show that the maximal efficacy of exercise for improving aerobic function is blunted by obesity. In addition, our preliminary data show a potential dose-response benefit of concomitant fat loss on exercise-induced improvements in aerobic function. Thus, combining an exercise intervention with caloric restriction resulting in fat loss may be more efficacious for improving aerobic function than exercise alone in obese elderly, a population at high risk for disability. This study is a 3-arm, 5-month randomized, clinical trial in 180 older (65-79 yrs), obese (BMI=30-34.9 kg/m2), sedentary men and women designed to determine whether the amount of fat loss (achieved through controlled underfeeding) affects the magnitude of improvement in aerobic function (maximal aerobic capacity and endurance) in response to a standardized exercise training stimulus that follows current recommendations. Participants will be randomized to an exercise training intervention (moderate-intensity treadmill walking, 4 d/wk) alone (EX Only), exercise with moderate caloric restriction (-250 kcal/d deficit) designed for low fat loss (EX+Low CR; ~3.4 kg fat loss), or exercise with intensive caloric restriction (-750 kcal/d deficit) designed for high fat loss (EX+High CR; ~10.2 kg fat loss). The Specific Aims are to determine the effects of adding moderate and intensive caloric restriction to a standardized aerobic exercise training intervention on: 1) maximal aerobic capacity and walking endurance (6-minute walking distance); 2) cardiovascular disease risk factors (inflammatory markers, blood lipids, blood pressure, glucose tolerance and endothelial function); and 3) inter- muscular, abdominal visceral and pericardial fat volumes. We will also determine whether improvements in aerobic function and CVD risk factors are related to the degree of total and regional fat loss. If our hypotheses are confirmed, this study will provide the first prospective and definitive evidence from a randomized, controlled trial that loss of fat mass augments exercise-induced improvements in aerobic function. These findings will provide persuasive evidence that addition of caloric restriction to an exercise intervention in older, obese adults may be more effective for improving aerobic function than exercise alone, and are likely to change traditional reluctance to recommend some caloric restriction during an exercise program in older adults for the purpose of maximizing their exercise efforts. In addition, by assessing lipid accumulation around visceral organs, and skeletal and cardiac muscle, before and after the interventions, we will also be able to determine the contribution of fat loss in these local depots to the magnitude of exercise-induced improvement in both functional and CVD risk factor outcomes. PUBLIC HEALTH RELEVANCE: This study will determine whether older, obese men and women who lose more fat during an exercise training program will experience greater improvements in fitness and endurance as a result of the exercise training than those who do not lose any fat, or very little fat. This knowledge could lead to a stronger clinical recommendation for inclusion of weight loss to benefit obese, older individuals who exercise. The results will also provide information on whether the location of fat loss is important for improving fitness and cardiovascular disease risk.