Contribution of Organ Size to Adaptive Thermogenesis during Caloric Restriction

热量限制期间器官大小对适应性产热的贡献

• 批准号: 8576836
• 负责人: WEI SHEN
• 金额: $ 20.26万
• 依托单位: ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8576836
• 关键词: Accounting; Adipose tissue; Adult; Aging; Biological; Biomedical Research; Body Composition; Body Size; Body Weight; Body Weight decreased; Brain; Brown Fat; Caloric Restriction; Data; Data Set; Databases; Deposition; Elements; Energy Metabolism; Equilibrium; Excision; Fatty acid glycerol esters; Future; Gastrointestinal tract structure; Grouping; Health; Heart; Hepatic Mass; Hormones; Hour; Indirect Calorimetry; Individual; Intervention; Kidney; Knowledge; Leptin; Level of Evidence; Liver; Longevity; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Metabolism; Mitochondria; Modeling; Obesity; Organ; Organ Size; Pancreas; Play; Regulation; Research; Research Personnel; Resolution; Rest; Role; Skeletal Muscle; Sleep; Spleen; Stress; Sympathetic Nervous System; Testing; Thermogenesis; Thyroid Hormones; Time; Tissues; Translations; Variant; Weight; base; improved; in vivo; model design; oxidative damage; sedentary

DESCRIPTION (provided by applicant): Adaptive thermogenesis is defined as the decrease in resting energy expenditure (REE) with caloric restriction beyond that which is expected based on changes in body mass and composition. Accurate quantification of adaptive thermogenesis requires precise measurements of heterogeneous body composition components. Most commonly used models designed to predict REE group body components into fat mass and fat free mass (FFM). However, the constituents of FFM have a wide range of specific metabolic rates. For example, the metabolic rate of the kidneys and the liver are 33-fold and 15-fold higher than that of skeletal muscle. Organ size based REE prediction models are more accurate than FFM based models. Most previous weight loss studies that have investigated adaptive thermogenesis use FFM predicted energy expenditure. To date only one study has examined organ size change in short term weight loss (i.e., 3 months); it is currently unknown whether adaptive thermogenesis still exists in long term caloric restriction and weight stable conditions. Using the CALERIE dataset, it is possible for the first time to evaluate adaptive thermogenesis during long term caloric restriction both with weight loss (i.e., at year 1) and under weight stabl conditions (i.e., at year 2). In the CALERIE dataset of the Pennington Biomedical Research Center, the availability of both cellular level and tissue-organ level data related to adaptive thermogenesis allows for the translation of cellular findings to higher biological levels of organization. We will use whole body high resolution contiguous magnetic resonance imaging (MRI) to measure volumes of high-metabolic-rate organs including the brain, liver, spleen, pancreas, kidneys, heart, and digestive tracts. This accurate quantification of organ masses will allow for a more precise characterization of adaptive thermogenesis at the tissue-organ level. Furthermore, the availability of liver fat by in vivo magnetic resonance spectroscopy will allow the quantification of "fat free liver mass". This is critical to warrant accurate quantification ofthe metabolically active liver mass. This study will, for the first time, unite the cellular level evidnce with the tissue-organ level evidence of adaptive thermogenesis during long term caloric restriction. The proposed analyses will answer a question put forth by many investigators in obesity and aging research - what is the contribution of the different organs and tissues to the changes in energy expenditure at a new body weight equilibrium after weight loss. The present study will uniquely make an important contribution to one of the major proposed mechanisms for the increase in lifespan with a reduction of oxidative damage. The knowledge gained will pave the way for future studies to accurately evaluate mechanisms of adaptive thermogenesis independent of organ and tissue size. This collected knowledge will contribute to developing interventions and strategies that can sustain weight loss and improve lifespan.

描述(由申请人提供)：适应性生热的定义是静息能量消耗(REE)的减少，热量限制超过了基于身体质量和成分变化的预期。适应生热作用的准确量化需要对不同的身体成分进行精确的测量。最常用的模型被设计来预测REE组身体成分为脂肪质量和无脂肪质量(FFM)。然而，FFM的成分具有广泛的特定代谢率。例如，肾脏和肝脏的代谢率分别是骨骼肌的33倍和15倍。基于器官大小的REE预测模型比基于FFM的模型更准确。大多数先前研究适应性产热的减肥研究都使用FFM来预测能量消耗。到目前为止，只有一项研究考察了短期体重减轻(即3个月)时器官大小的变化；目前尚不清楚在长期热量限制和体重稳定的条件下，适应性产热是否仍然存在。使用CALERIE数据集，第一次有可能评估长期热量限制期间的适应性生热作用，包括体重减轻(即在第1年)和在体重稳定条件下(即在第2年)。在彭宁顿生物医学研究中心的CALERIE数据集中，与适应性产热相关的细胞水平和组织器官水平的数据的可用性允许将细胞发现转化为更高生物水平的组织。我们将使用全身高分辨率连续磁共振成像(MRI)来测量包括脑、肝、脾、胰腺、肾脏、心脏和消化道在内的高代谢率器官的体积。这种对器官质量的准确量化将允许在组织器官水平上更准确地描述适应性产热作用。此外，通过体内磁共振波谱获得肝脏脂肪将使“无脂肪肝脏质量”的量化成为可能。这对于保证代谢活跃的肝脏质量的准确量化是至关重要的。这项研究将首次将细胞水平的证据与组织器官水平的证据结合起来，证明长期热量限制下的适应性产热。拟议的分析将回答肥胖和衰老研究中许多研究人员提出的一个问题--减肥后不同器官和组织对新体重平衡时能量消耗的变化有何贡献。这项研究将独一无二地对主要的拟议机制之一作出重要贡献，以减少氧化损伤，延长寿命。所获得的知识将为未来的研究铺平道路，以准确评估不依赖于器官和组织大小的适应性产热机制。收集到的这些知识将有助于制定能够持续减肥和延长寿命的干预措施和战略。