Effects of Aerobic Exercise on Skeletal Muscle Remodeling in Colon Cancer

项目摘要/摘要 诊断后体力活动与结肠癌癌症复发和死亡的低风险相关 幸存者。然而，支持体力活动对癌症影响的生物学机制 人们对复发和死亡知之甚少。骨骼肌是人体内最丰富的组织， 相当于体重的40%和基础能量消耗的30%。骨骼肌脂肪渗透，已知 作为肌骨病，是一种异位的甘油三酯储存库，会导致胰岛素抵抗和炎症。每三个人中有一个 结肠癌幸存者患有肌骨瘤病。肌瘤病增加癌症复发、心血管疾病的风险 结肠癌幸存者的疾病和死亡。在老年人中，肌肉瘤预示着肌肉力量不足。 以及随后的残疾，这是相关的，因为62%的结肠癌幸存者有功能障碍， 这些限制侵蚀了生活质量，影响了寿命。我们假设有组织的锻炼 训练重塑骨骼肌组成(目标1)，纠正肌肉代谢不灵活(目标2)，以及 增加肌肉功能(目标3)，与改善癌症预后和降低风险相一致 发病率和死亡率之间的矛盾。响应PAR-18-893《体力活动和体重控制》 癌症幸存者的干预：对预后和生存的生物标记物的影响，“我们将进行 对138例I-III期结肠癌幸存者进行结构化有氧运动训练的随机对照试验。 受试者将通过路易斯安那州肿瘤登记中心招募，这是一个由美国国家癌症研究所资助的基于人群的登记机构 监测、流行病学和最终结果(SEER)方案，以反映儿童的社会经济多样性 区域。受试者将被随机分为伸展注意力对照组或225分钟/周的中等强度有氧运动 锻炼(70%心率储备)12周。目标1将检验有氧运动减少的假设 使用全身磁共振成像测量全身肌肉间脂肪组织。目标2将 验证有氧运动降低餐后甘油三酯浓度并增加游离的假设 使用含有[U-13C]棕榈酸酯的同位素标记液体混合餐测量脂肪酸氧化。目标 3将检验有氧运动增加腿部骨骼肌力和体力的假设 功能使用Biodex测力和10步爬楼梯功率。肌瘤病是一种常见的疾病 结肠癌幸存者的健康状况。确定体力活动促进健康的机制将 促进以患者为中心的精准运动处方，并被证明具有较高的 临床益处。拟议的AIMS将利用跨学科团队的协同效应来提供全面的 并明确了体力活动与癌症预后在交界处的新生物学机制 肌肉生理学和脂肪细胞生物学。

PROJECT SUMMARY/ABSTRACT Postdiagnosis physical activity is associated with a lower risk of cancer recurrence and death in colon cancer survivors. However, the biological mechanisms that underpin the effects of physical activity on cancer recurrence and death are poorly understood. Skeletal muscle is the most abundant tissue in the human body, representing 40% of body weight and 30% of basal energy expenditure. Skeletal muscle fat infiltration, known as myosteatosis, is an ectopic triglyceride depot that causes insulin resistance and inflammation. One in three colon cancer survivors has myosteatosis. Myosteatosis increases the risk of cancer recurrence, cardiovascular disease, and death in colon cancer survivors. Among older adults, myosteatosis predicts poor muscle strength and subsequent disability, which is relevant because 62% of colon cancer survivors have functional limitations, and these limitations erode quality of life and compromise longevity. We hypothesize that structured exercise training remodels skeletal muscle composition (Aim 1), corrects muscle metabolic inflexibility (Aim 2), and increases muscle function (Aim 3) in a manner consistent with an improved cancer prognosis and reduced risk of competing morbidity and mortality. In response to PAR-18-893 "Physical Activity and Weight Control Interventions Among Cancer Survivors: Effects on Biomarkers of Prognosis and Survival," we will conduct a randomized controlled trial of structured aerobic exercise training in 138 stage I-III colon cancer survivors. Subjects will be recruited using the Louisiana Tumor Registry, a population-based registry funded by the NCI’s Surveillance, Epidemiology and End Results (SEER) Program to reflect the socioeconomic diversity of the region. Subjects will be randomized to stretching attention control or 225 min/wk of moderate-intensity aerobic exercise (70% heart rate reserve) for 12-weeks. Aim 1 will test the hypothesis that aerobic exercise decreases whole-body intermuscular adipose tissue measured using whole-body magnetic resonance imaging. Aim 2 will test the hypothesis that aerobic exercise decreases postprandial triglyceride concentration and increases free fatty acid oxidation measured using an isotopically labeled liquid mixed meal containing [U-13C]palmitate. Aim 3 will test the hypothesis that aerobic exercise increases lower extremity skeletal muscle strength and physical function using Biodex dynamometry and 10-step stair climb power. Myosteatosis is common and compromises the health of colon cancer survivors. Identifying the health-promoting mechanisms of physical activity would facilitate precision exercise prescriptions that are patient-centered and proven to have a high probability of clinical benefit. The proposed aims will leverage a transdisciplinary team's synergies to offer comprehensive and definitive insight into a novel biological mechanism of physical activity and cancer prognosis at the junction of muscle physiology and adipocyte biology.