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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

基本信息

批准号：
10630967
负责人：
Justin C Brown
金额：
$ 60.14万
依托单位：
LSU PENNINGTON BIOMEDICAL RESEARCH CTR
依托单位国家：
美国
项目类别：
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/10630967
关键词：
Adipose tissue Aerobic Exercise Ankle Biological Body Weight Cancer Prognosis Cancer Survivor Carbon Dioxide Cardiovascular Diseases Certification Cessation of life Clinical Colon Carcinoma Control Groups Counseling Data Diagnosis 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 Modeling 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 Recurrent Malignant Neoplasm 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

项目摘要

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。