Effects of Aerobic Exercise on Skeletal Muscle Remodeling in Colon Cancer

有氧运动对结肠癌骨骼肌重塑的影响

• 批准号: 10416320
• 负责人: Justin C Brown
• 金额: $ 61.32万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-03 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10416320
• 关键词: Adipose tissue; Aerobic Exercise; Ankle; Biological; Body Weight; Cancer Prognosis; Cancer Survivor; Carbon Dioxide; Cardiovascular Diseases; Cessation of life; Clinical; Colon Carcinoma; Control Groups; Counseling; Data; Elderly; Energy Metabolism; Exercise; Fatty Acids; Fatty acid glycerol esters; Funding; Glycerol; Health; Health Promotion; Heart Rate; Home; Human body; Impairment; Infiltration; Inflammation; Insulin Resistance; Intervention; Isometric Exercise; Isotonic Exercise; Isotope Labeling; Isotopes; Knee; Liquid substance; Liver; Longevity; Louisiana; Lower Extremity; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Metabolic; Metabolism; Morbidity - disease rate; Muscle; Muscle function; Nonesterified Fatty Acids; Obesity; Oncology; Palmitates; Pathway interactions; Physical Function; Physical activity; Population-Based Registry; Probability; Prognosis; Quality of life; Randomized; Randomized Controlled Trials; Risk; SEER Program; Series; Skeletal Muscle; Stretching; Structure; Study Subject; Techniques; Telephone; Testing; Tissues; Triglycerides; Visceral fat; Weight maintenance regimen; adipocyte biology; attentional control; behavior change; cancer recurrence; cancer risk; digital; disability; exercise adherence; exercise physiologist; exercise prescription; exercise training; fatty acid metabolism; fatty acid oxidation; heart rate monitor; improved; insight; metabolic phenotype; mortality; muscle physiology; muscle strength; novel; oxidation; patient oriented; physical inactivity; prognosis biomarker; recruit; response; secondary analysis; socioeconomic diversity; synergism; treadmill; tumor registry; uptake; video chat

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.

项目概要/摘要 诊断后体力活动与结肠癌癌症复发和死亡风险降低相关 幸存者。然而，支持体力活动对癌症影响的生物学机制 对复发和死亡知之甚少。骨骼肌是人体中最丰富的组织， 占体重的40%和基础能量消耗的30%。已知骨骼肌脂肪浸润 肌脂肪变性是一种异位甘油三酯储存库，会导致胰岛素抵抗和炎症。三分之一 结肠癌幸存者患有肌脂肪变性。肌脂肪变性增加癌症复发、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，肌脂肪变性预示着肌肉力量较差 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限制， 这些限制会降低生活质量并影响寿命。我们假设结构化锻炼 训练重塑骨骼肌组成（目标 1），纠正肌肉代谢僵化（目标 2），以及 以与改善癌症预后和降低风险一致的方式增强肌肉功能（目标 3） 相互竞争的发病率和死亡率。响应 PAR-18-893“体力活动和体重控制 癌症幸存者的干预措施：对预后和生存的生物标志物的影响”，我们将进行 对 138 名 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处招募，这是一个由 NCI 资助的基于人群的登记处 监测、流行病学和最终结果 (SEER) 计划，反映社会经济多样性 地区。受试者将被随机分配接受伸展注意力控制组或每周 225 分钟的中等强度有氧运动组 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间脂肪组织。目标2将 检验有氧运动降低餐后甘油三酯浓度并增加游离甘油三酯的假设 使用含有[U-13C]棕榈酸酯的同位素标记液体混合粉测量脂肪酸氧化。目的 3 将检验有氧运动增加下肢骨骼肌力量和体力的假设 使用 Biodex 测力法和 10 步爬楼梯功率的功能。肌脂肪变性很常见并且会造成损害 结肠癌幸存者的健康。确定身体活动促进健康的机制将 促进以患者为中心的精确运动处方，并被证明有很高的可能性 临床获益。拟议的目标将利用跨学科团队的协同作用来提供全面的 并对体力活动和癌症预后的新生物学机制有明确的见解 肌肉生理学和脂肪细胞生物学。