Revving-Up Exercise for Sustained Weight-Loss by Altering Neurological Reward & D

通过改变神经奖励来加速运动以实现持续减肥

• 批准号: 8708006
• 负责人: Nora L. Nock
• 金额: $ 49.64万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8708006
• 关键词: Adult; Animals; Appetitive Behavior; Area; Automobile Driving; Behavior Therapy; Behavioral; Biological Markers; Body Composition; Body Weight decreased; Body fat; Brain; Brain region; Brain-Derived Neurotrophic Factor; Cancer Patient; Cancer Survivor; Cardiovascular Diseases; Cessation of life; Chronic; Climacteric; Comorbidity; Corpus striatum structure; Cues; Death Rate; Dopamine; Dopamine Agonists; Dorsal; Eating; Eating Behavior; Endometrial Carcinoma; Exercise; Feasibility Studies; Female; Food; Functional Magnetic Resonance Imaging; Goals; Human; Hyperphagia; Image; Incentives; Individual; Intervention; Lead; Leptin; Life Style; Localized Disease; Malignant Neoplasms; Mechanics; Motivation; Motor; Neurologic; Neurons; Non obese; Obesity; Operative Surgical Procedures; Outcome; Parkinson Disease; Patient Self-Report; Patients; Pattern; Physiological; Population; Property; Public Health; Quality of life; Randomized; Rewards; Risk Factors; Satiation; Signal Transduction; Stimulus; System; Time; Weight; Woman; adipokines; anticancer research; cancer diagnosis; carcinogenesis; executive function; fitness; hedonic; high risk; improved; lifestyle intervention; mortality; motor control; neurobehavioral; neurotrophic factor; novel; primary outcome; public health relevance; randomized trial; relating to nervous system; response; tumor progression

DESCRIPTION (provided by applicant): Obesity is one of the greatest public health challenges of our nation and a leading risk factor for endometrial cancer (EC), particularly Type I forms, that are increasing. Although death rates from most cancers have been decreasing, overall mortality in EC patients is increasing. EC survivors have a high rate of obesity (38 percent-65 percent) and, obese EC patients have the highest risk of death among all cancers. Unlike other cancer survivors, EC survivors do not typically make spontaneous lifestyle changes during the 'teachable moment' of a cancer diagnosis. EC survivors' poor fitness levels and surgical treatments may make weight loss particularly challenging. However, only two prior lifestyle interventions have focused on EC survivors. In animals, high intensity exercise has been show to increase neurotrophins and reward via altered striatal dopamine. In humans, chronic high intensity exercise enhances meal satiety and may reduce hedonic eating. We have shown that 'assisted' exercise, a mode of exercise whereby the patients' voluntary exercise rate is augmented mechanically, improves motor control and has activation patterns consistent with modulation of brain dopamine levels in Parkinson's Disease patients. In a feasibility study, we evaluated the 'assisted' exercise paradigm in obese EC survivors and found that 'assisted' exercise improves fitness levels, body composition, exercise motivation and eating behavior. No prior studies have evaluated the effects of 'assisted' exercise on appetitive behavior in any population. We propose a novel transdisciplinary randomized trial to evaluate the effects of six months of 'assisted' and voluntary rate exercise on physiological and behavioral outcomes as well as neuronal activity in response to food cues in obese EC survivors. The overarching goal is to show that obese EC survivors performing 'assisted' exercise will have improved eating behavior, exercise motivation and quality of life (QoL) as well as reduced neuronal activation in brain regions associated with food reward and motivation in response to high-calorie food images compared to patients performing voluntary rate exercise that will be sustained after the intervention. In Specific Aim 1, we will evaluate physiological (weight, body fat, fitness) and behavioral (eating behavior, exercise motivation, QoL) changes in obese EC patients randomized to perform 24 'assisted' or voluntary rate cycling at baseline, end of treatment (EOT) and 24 weeks post-EOT (EOT+24). In Specific Aim 2, we will evaluate neuronal response to high-calorie food images and a stop signal task in brain regions associated with reward, motivation and inhibitory control using functional magnetic resonance imaging in obese EC patients performing 'assisted' or voluntary rate exercise at baseline, EOT and EOT+24. In Specific Aim 3, we will evaluate changes in circulating neutrophins (e.g., BDNF) and adipokines (e.g., leptin) in both groups at baseline, EOT and EOT+24. The proposed 'assisted' exercise intervention has the potential to lead to improved survival in obese EC patients as well as other obese individuals with and without cancer.

描述（由申请人提供）：肥胖是我国最大的公共卫生挑战之一，也是子宫内膜癌 (EC)（尤其是 I 型子宫内膜癌）的主要危险因素 形式，且不断增加。尽管大多数癌症的死亡率一直在下降，但 EC 患者的总体死亡率却在上升。 EC幸存者的肥胖率很高（38%-65%），并且肥胖的EC患者的死亡风险是所有癌症中最高的。与其他癌症幸存者不同，EC 幸存者通常不会在癌症诊断的“受教育时刻”自发改变生活方式。 EC 幸存者较差的健康水平和手术治疗可能使减肥变得尤其困难。然而，之前只有两项生活方式干预措施关注 EC 幸存者。在动物中，高强度运动已被证明可以通过改变纹状体多巴胺来增加神经营养素和奖励。对于人类来说，长期高强度运动会增强膳食饱腹感，并可能减少享乐性饮食。我们已经证明，“辅助”运动是一种机械地提高患者自主运动频率的运动模式，可以改善运动控制，并具有与帕金森病患者大脑多巴胺水平调节一致的激活模式。在一项可行性研究中，我们评估了肥胖 EC 幸存者的“辅助”运动范例，发现“辅助”运动可以改善健康水平、身体成分、运动动机和饮食行为。之前没有研究评估“辅助”运动对任何人群食欲行为的影响。我们提出了一项新颖的跨学科随机试验，以评估六个月的“辅助”和自愿速率运动对肥胖 EC 幸存者的生理和行为结果以及响应食物线索的神经元活动的影响。总体目标是表明，与干预后进行自愿速率运动的患者相比，进行“辅助”运动的肥胖 EC 幸存者将改善饮食行为、运动动机和生活质量 (QoL)，并减少与食物奖励和响应高热量食物图像的动机相关的大脑区域的神经元激活。在具体目标 1 中，我们将评估肥胖 EC 患者在基线、治疗结束 (EOT) 和 EOT 后 24 周 (EOT+24) 时随机进行 24 次“辅助”或自愿频率循环的生理（体重、体脂、健康）和行为（饮食行为、运动动机、生活质量）变化。在具体目标 2 中，我们将使用功能磁共振成像，在基线、EOT 和 EOT+24 进行“辅助”或自愿速率运动的肥胖 EC 患者中，评估与奖励、动机和抑制控制相关的大脑区域对高热量食物图像和停止信号任务的神经元反应。在具体目标 3 中，我们将评估两组在基线、EOT 和 EOT+24 时循环中性粒细胞（例如 BDNF）和脂肪因子（例如瘦素）的变化。拟议的“辅助”运动干预有可能提高肥胖 EC 患者以及其他患有或未患有癌症的肥胖个体的生存率。