ENERGY BALANCE AND SUBSTRATE METABOLISM

能量平衡和底物代谢

• 批准号: 6344585
• 负责人: Joseph W. Kemnitz
• 金额: $ 35.36万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6344585
• 关键词: Macaca mulatta; adipose tissue; aging; bioenergetics; biological models; biopsy; blood glucose; blood lipoprotein metabolism; body composition; caloric dietary content; calorimetry; carbohydrate metabolism; computed axial tomography; dietary restriction; glucose clamp technique; glucose tolerance test; high density lipoproteins; insulin receptor; insulin sensitivity /resistance; isotope dilution method; longitudinal animal study; nutrition related tag; photon absorptiometry; striated muscles; very low density lipoprotein

Beneficial alterations in energy expenditure, glucose metabolism, and cardiovascular health could be major contributors to the life-extending action of dietary restriction. We have shown that dietary restriction causes significant change sin all three of these areas in rhesus monkeys. Long-term changes in one or more of these areas could be extremely important to the overall effect of this intervention. We hypothesize that dietary restriction causes sustained changes in energy expenditure, glucose metabolism, and cardiovascular health which contribute to the retardation of disease and aging. In this renewal, we plan to continue investigating the effect of aging and dietary restriction on composition, we plan to continue measuring changes in body lean and fat mass with aging and dietary body mass. This will be done using several techniques including anthropometrics, dual-energy x-ray absorptiometry (DXA), computer assisted tomography (CT) and isotope dilution. Specific Aim 2 is to determine the effect of dietary restriction of whole-animal energy expenditure. Energy expenditure will be measured by indirect respiration calorimetry using calorimetry chambers and the doubly labeled water method. The calorimetry experiments will provide estimates of resting energy expenditure, the themic effect of feeding, activity, and total energy expenditure. Body composition data will be used to normalized energy expenditure for comparison between groups and among individuals. In addition to calorimetry derived measurements of activity, motion detectors will be used for further quantification of physical activity. Specific Aim 3 is to elucidate the effect of dietary restriction on insulin sensitivity and other parameters of glucose regulation by Minimal Modeling and quantitation of insulin receptor abundance. Minimal Modeling is performed on data derived from a frequently sampled intravenous glucose tolerance test and insulin receptor abundance will be measured in biopsies of skeletal muscle. In Specific Aim 4, we will further examine the effects of dietary restriction on composition and properties of plasma LDL that may affect their proteoglycan-binding and thus their atherogenicity, using blood samples, and in vitro systems for assessment.

能源消耗，葡萄糖代谢和心血管健康的有益改变可能是饮食限制生命延长行动的主要因素。 我们已经表明，饮食限制会引起重大变化的罪恶，这三个在恒河猴中的三个地区。这些领域中一个或多个的长期变化对于这种干预的总体影响可能非常重要。我们假设饮食限制会导致能量消耗，葡萄糖代谢和心血管健康的持续变化，这会导致疾病和衰老的延迟。 在这种续约中，我们计划继续研究衰老和饮食限制对成分的影响，我们计划继续测量体内瘦肉和脂肪质量的变化，并随着衰老和饮食体重的体重来衡量。 这将使用几种技术，包括拟人化，双能X射线吸收法（DXA），计算机辅助断层扫描（CT）和同位素稀释。 具体目的2是确定全面能量消耗的饮食限制的影响。 能量消耗将通过使用量热法室和双重标记的水方法来测量通过间接呼吸量热法测量。量热法实验将提供静息能量消耗，喂养，活动和总能量消耗的主题效果的估计。 人体组成数据将用于归一化能量消耗，以在组之间和个体之间进行比较。 除了量热法衍生的活动测量外，运动探测器还将用于进一步量化体育活动。 具体目的3是通过最小的建模和胰岛素受体丰度的定量来阐明饮食限制对胰岛素敏感性和葡萄糖调节的其他参数的影响。 对从经常采样的静脉内葡萄糖耐量测试得出的数据进行最小的建模，并将在骨骼肌活检中测量胰岛素受体丰度。 在特定的目标4中，我们将进一步研究饮食限制对可能影响其蛋白聚糖结合的血浆LDL组成和特性的影响，从而使用血液样本和体外系统进行评估。