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

描述（由申请人提供）：衰老与有氧能力、运动耐受性和功能耐力的下降有关，从而导致身体残疾。到目前为止，有规律的运动是唯一能持续改善有氧功能的疗法，也许还能延缓残疾的发生。然而，一些数据表明，运动对改善有氧功能的最大功效被肥胖削弱了。此外，我们的初步数据显示，伴随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，结合运动干预和热量限制导致的脂肪减少可能比单独运动更有效地改善肥胖老年人的有氧功能，这是一个高风险的残疾人群。本研究是一项3组、5个月的随机临床试验，在180名老年人（65-79岁）、肥胖（BMI=30-34.9 kg/m2）、久坐不动的男性和女性中进行，旨在确定脂肪减少的数量（通过控制进食不足实现）是否影响有氧功能（最大有氧能力和耐力）改善的程度，以响应标准化的运动训练刺激，遵循目前的建议。参与者将被随机分配到单独的运动训练干预（中等强度的跑步机行走，4天/周）（仅限EX），中等热量限制运动（-250千卡/天赤字）设计用于低脂肪减少（EX+低CR； ~3.4公斤脂肪减少），或高热量限制运动（-750千卡/天赤字）设计用于高脂肪减少（EX+高CR； ~10.2公斤脂肪减少）。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)心血管疾病危险因素（炎症标志物、血脂、血压、糖耐量和内皮功能）；3)肌肉间、腹部内脏和心包脂肪量。我们还将确定有氧功能和心血管疾病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，这项研究将提供第一个前瞻性和明确的证据，来自一项随机对照试验，即脂肪量的减少可以增强运动引起的有氧功能的改善。这些发现将提供有说服力的证据，证明在老年人的运动干预中增加热量限制可能比单独运动更有效地改善有氧功能，并可能改变传统上不愿在老年人的运动计划中推荐一些热量限制，以最大限度地提高他们的运动效果。此外，通过评估干预前后内脏器官、骨骼肌和心肌周围的脂质积累，我们还将能够确定这些局部仓库的脂肪减少对运动诱导的功能和心血管疾病危险因素结果改善的程度的贡献。公共健康相关性：这项研究将确定在运动训练项目中减掉更多脂肪的老年肥胖男性和女性是否会比那些没有减掉任何脂肪或脂肪很少的人在运动训练中获得更大的健康和耐力改善。这一认识可能会导致更强有力的临床建议，包括减肥，有利于肥胖的老年人锻炼。研究结果还将提供信息，说明脂肪减少的位置对改善健康和心血管疾病风险是否重要。

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.