Novel Roles of Adipose Tissue in Exercise Training Effects on Glucose Homeostasis

脂肪组织在运动训练中的新作用对血糖稳态的影响

• 批准号: 8061439
• 负责人: Kristin I Stanford
• 金额: $ 4.76万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8061439
• 关键词: Novel; Roles; Adipose; Tissue; Exercise

DESCRIPTION (provided by applicant): Chronic exercise training, consisting of repeated bouts of exercise over a sustained period, has undisputed effects to improve whole-body glucose homeostasis and insulin sensitivity, adaptations critical for people with diabetes. While these beneficial adaptations to training are well described, the underlying cellular and molecular mechanisms are not fully understood. Although the effects of exercise training have largely been investigated in the context of adaptations to skeletal muscle, there has been little investigation into the role that other tissues may play in mediating the effects of exercise training on glucose homeostasis. Our preliminary data show that transplantation of subcutaneous white adipose tissue from exercise trained mice dramatically improves glucose tolerance, well above what occurs in adipose tissue transplanted from untrained animals. This effect is short-lived, present at 9 days post-transplantation and gone by 6 weeks. Based on these findings, this project is designed to test the novel hypothesis that exercise training causes adaptations to white adipose tissue that in turn function in a paracrine manner to improve whole-body and muscle glucose homeostasis. There are three specific aims: 1) Determine the effects of transplanting adipose tissue from exercise trained mice on whole-body glucose homeostasis and insulin sensitivity; 2) Determine if adipose tissue from exercise trained mice has paracrine effects to increase glucose uptake in skeletal muscle; 3) Identify adipokines from the adipose tissue of exercise trained mice that function to improve whole-body and skeletal muscle glucose metabolism. This project should identify novel adipocyte-derived factors that function to mediate the beneficial effects of exercise training on glucose homeostasis. These studies have the potential to significantly impact the treatment of obesity and type 2 diabetes. PUBLIC HEALTH RELEVANCE: Diabetes is a major public health concern and exercise has an undisputed role in the treatment and prevention of this disease. The goal of this research proposal is to discover how exercise training causes fundamental changes to adipose tissue that signal the body to improve glucose metabolism. This will lead to a better understanding of the beneficial effects of exercise in diabetes and could help to identify novel therapies for diabetes.

描述（由申请人提供）：慢性运动训练，包括在持续的时期内反复进行运动，对改善全身葡萄糖稳态和胰岛素敏感性具有无可争议的效果，对糖尿病患者至关重要。虽然这些对训练的有益适应性得到很好的描述，但尚未完全了解潜在的细胞和分子机制。尽管在适应骨骼肌的背景下，在很大程度上研究了运动训练的影响，但几乎没有研究其他组织在介导锻炼训练对葡萄糖稳态的影响中所起的作用。我们的初步数据表明，从运动训练的小鼠中对皮下白色脂肪组织移植可显着提高葡萄糖耐受性，远高于未经训练的动物移植的脂肪组织中发生的葡萄糖耐受性。这种效果是短暂的，在移植后9天存在，并消失了6周。基于这些发现，该项目旨在检验新的假设，即运动训练会导致对白脂肪组织的适应，而白脂肪组织又以旁分泌方式发挥作用，以改善全身和肌肉葡萄糖稳态。有三个特定的目的：1）确定运动训练的小鼠对全身葡萄糖稳态和胰岛素敏感性的移植脂肪组织的影响； 2）确定来自运动训练的小鼠的脂肪组织是否具有旁分泌作用，以增加骨骼肌的葡萄糖摄取； 3）从运动训练的小鼠的脂肪组织中鉴定脂肪因子，以改善全身和骨骼肌葡萄糖代谢。该项目应确定脂肪细胞衍生的新型因素，这些因素可以介导运动训练对葡萄糖稳态的有益作用。这些研究有可能显着影响肥胖症和2型糖尿病的治疗。 公共卫生相关性：糖尿病是一个主要的公共卫生问题，运动在治疗和预防这种疾病中无可争议的作用。这项研究建议的目的是发现运动训练如何导致脂肪组织的基本变化，以提示人体改善葡萄糖代谢。这将使人们更好地了解运动对糖尿病的有益作用，并有助于鉴定糖尿病的新疗法。