Effect of exercise and weight loss on adipose tissue biology

描述(申请人提供)：较高的体力活动水平和较低的体重或体脂与几种癌症的风险降低有关，特别是结直肠癌和绝经后乳腺癌。这种联系的可能机制包括炎症因子、类固醇激素、胰岛素样生长因子或胰岛素抵抗，以及脂代谢。这些机制中的许多都可以通过能量平衡的变化来调节，例如体重变化或身体成分变化。脂肪组织在几种已提出的机制中发挥了作用，特别是通过产生促炎细胞因子和性激素。这项拟议的项目将研究能量平衡，特别是饮食、体力活动和体重变化与脂肪组织生物学之间的交叉。这将是一项资助的人类临床试验的辅助，该试验针对超重或肥胖、以前久坐不动的绝经后女性进行锻炼和限制卡路里。该项目将在60名妇女中收集腹部皮下脂肪组织样本，基线和6个月时。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)对脂肪组织中特异性促炎细胞因子(即IL6和TNF1)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(即芳香酶)的表达的影响；(2)探讨体重(Kg)或体重指数(kg/m2)和体力活动(METhoursWeek)的变化对上述生物标志物的影响；(3)利用Affymetrix U133 plus 2.0基因芯片研究脂肪组织基因表达谱的变化，重点关注运动节食组(n=10)和对照组(n=10)参与者的子集。预计运动节食组的体脂百分比变化最大，因此提供了最强烈的对比。据我们所知，这项研究将是第一个随机对照试验，测试运动对人类皮下脂肪组织中mRNA和蛋白质表达的影响，无论是单独运动还是与限制卡路里的饮食相结合。能量平衡越来越被认为是癌症风险的一个重要因素。脂肪细胞处于能量平衡和假设的能量平衡与致癌机制之间的联系的交界处。对脂肪组织的检查对于进一步了解这一联系至关重要。这项试验将提供生活方式干预对脂肪组织生物学重要方面的影响的数据。项目简介本项目将调查饮食和锻炼对脂肪组织的影响。身体不活动、超重或肥胖与患某些癌症的风险增加有关。因此，我们想了解体育活动、低卡路里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有关的生物因素。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。

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.