Effect of exercise and weight loss on adipose tissue biology

运动和减肥对脂肪组织生物学的影响

• 批准号: 7615661
• 负责人: Anne M. McTiernan
• 金额: $ 23.76万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615661
• 关键词: Abdomen; Adipose tissue; Androgens; Aromatase; Biological Factors; Biological Markers; Biology; Body Composition; Body Weight; Body Weight Changes; Body Weight decreased; Body fat; Body mass index; Caloric Restriction; Calories; Clinical Trials; Colorectal; Data; Diet; Exercise; Fatty acid glycerol esters; Funding; Gene Chips; Gene Expression; Gonadal Steroid Hormones; Hour; Human; Inflammatory; Insulin; Insulin Resistance; Knowledge; Leptin; Life Style; Link; Malignant Neoplasms; Mediating; Messenger RNA; Obesity; Overweight; Participant; Pathway interactions; Pattern; Physical activity; Play; Postmenopause; Production; Randomized Controlled Trials; Recommendation; Risk; Role; Somatomedins; Testing; Tissue Sample; Tissues; Woman; adipokines; adiponectin; base; cancer risk; cancer type; carcinogenesis; cytokine; diet and exercise; dietary restriction; energy balance; lifestyle intervention; lipid metabolism; mRNA Expression; malignant breast neoplasm; protein expression; sedentary; steroid hormone; subcutaneous

DESCRIPTION (provided by applicant): Higher levels of physical activity and lower body weight or body fat are associated with a decreased risk of several types of cancer, in particular colorectal and postmenopausal breast cancer. Possible mechanistic pathways for this association involve inflammatory factors, steroid hormones, insulin like growth factors or insulin resistance, and lipid metabolism. Many of these mechanisms can be mediated by changes in energy balance such as weight change or changes in body composition. Adipose tissue plays a role in several of the proposed mechanisms, particularly via the production of proinflammatory cytokines and sex hormones. The proposed project will examine the intersection between energy balance specifically diet, physical activity and weight change and adipose tissue biology.There will be ancillary to a funded human clinical trial of exercise and caloric restriction in overweight or obese, previously sedentary, postmenopausal women. The project will collect subcutaneous abdominal adipose tissue sample sat base line and at 6 months in 60 women. Specific aims are (1) to investigate the effects of exercise (n=15), reduced calorie diet (n=15), exercise+diet (n=15) and usual lifestyle control (n=15) on adipose tissue mRNA and protein expression of specific proinflammatory cytokines (i.e.IL6andTNF1) and adipokines(i.e. leptin and adiponectin), as well as mRNA expression related to sex steroid hormone production (i.e. aromatase); (2) to investigate the impact of changes in body weight (kg) or body mass index (kg/m2) and physical activity (METhoursweek) on the above biomarkers ; and (3) to explore changes in adipose tissue gene expression patterns using the Affymetrix U133 plus 2.0 Gene Chip microarray ,focusing on a subset of participants in the exercise + diet group (n=10) versus controls (n=10). The exercise + diet group is expected to have the largest change in percent body fat, thus providing the strongest contrast. To our knowledge, this study will be the first randomized controlled trial to test the effects of exercise, both alone and in combination with a calorie restricted diet, on mRNA and protein expression in subcutaneous adipose tissue in humans. Energy balance is becoming increasingly recognized as an important factor in cancer risk. The adipocyteis at the interface of the association between energy balance and the hypothesized mechanisms linking energy balance to carcinogenesis. Examination of adipose tissue is critical to further the understanding of this link. This trial will provide data on the effect of a lifestyle intervention on important aspects of adipose tissue biology. PROJECT NARRATIVE This project will investigate the effects of diet and exercise on fat tissue. Being physically inactive and overweight or obese has been linked to increased risk of some cancers. Thus, we want to understand how physical activity, a diet low in calories, and body composition changes alter biological factors in fat tissue that are thought to be associated with cancer risk. This information will allow us to develop better lifestyle recommendations on how to reduce cancer risk.

描述（由申请人提供）：较高水平的体力活动和较低的体重或体脂与几种类型癌症的风险降低相关，特别是结肠直肠癌和绝经后乳腺癌。这种关联的可能机制途径涉及炎症因子、类固醇激素、胰岛素样生长因子或胰岛素抵抗和脂质代谢。这些机制中的许多都可以通过 通过能量平衡的变化，如体重变化或身体成分的变化。脂肪组织在几种提出的机制中发挥作用，特别是通过产生促炎细胞因子和性激素。拟议的项目将研究能量平衡，特别是饮食，身体活动和体重变化与脂肪组织生物学之间的交叉点。将辅助一项资助的超重或肥胖，以前久坐不动，绝经后妇女的运动和热量限制的人体临床试验。该项目将收集60名妇女在基线和6个月时的皮下腹部脂肪组织样本。具体目的是（1）研究运动（n=15）、低热量饮食（n=15）、运动+饮食（n=15）和日常生活方式控制（n=15）对脂肪组织特异性促炎细胞因子mRNA和蛋白表达的影响（即IL 6和TNF 1）和脂肪因子（即瘦素和脂联素），以及与性类固醇激素产生相关的mRNA表达（即芳香酶）;（2）研究体重（kg）或体重指数（kg/m2）和体力活动变化的影响（方法星期）对上述生物标志物的影响;和（3）使用AffyphineU 133 plus 2.0基因芯片微阵列探索脂肪组织基因表达模式的变化，重点关注运动+饮食组（n=10）与对照组（n=10）中的参与者子集。运动+饮食组预计在体脂百分比方面的变化最大，因此提供了最强的对比。据我们所知，这项研究将是第一个随机对照试验，以测试运动的影响，无论是单独的，并结合热量限制饮食，对人类皮下脂肪组织的mRNA和蛋白质表达。 能量平衡越来越被认为是癌症风险的重要因素。脂肪细胞处于能量平衡和假设的能量平衡与肿瘤发生之间联系的界面。脂肪组织的检查对于进一步理解这一联系至关重要。这项试验将提供有关生活方式干预对脂肪组织生物学重要方面影响的数据。项目叙述本项目将调查饮食和运动对脂肪组织的影响。缺乏运动、超重或肥胖与某些癌症的风险增加有关。因此，我们想了解身体活动，低热量饮食和身体成分的变化如何改变脂肪组织中被认为与癌症风险相关的生物因素。这些信息将使我们能够就如何降低癌症风险制定更好的生活方式建议。