Contribution of Organ Size to Adaptive Thermogenesis during Caloric Restriction

描述（由申请人提供）：适应性产热被定义为静息能量消耗（REE）的减少，热量限制超出了基于体重和成分变化的预期。准确量化适应性产热需要精确测量异质体成分。最常用的模型用于预测REE组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REE的器官大小预测模型比基于FFM的预测模型更准确。以前大多数研究适应性产热的减肥研究都使用FFM预测能量消耗。迄今为止，只有一项研究检查了短期体重减轻（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。利用CALERIE数据集，首次有可能评估长期热量限制期间体重减轻（即第1年）和体重稳定条件下（即第2年）的适应性产热。在Pennington生物医学研究中心的CALERIE数据集中，细胞水平和组织器官水平的适应性产热相关数据的可用性允许将细胞发现转化为更高的生物组织水平。我们将使用全身高分辨率连续磁共振成像（MRI）来测量高代谢率器官的体积，包括大脑、肝脏、脾脏、胰腺、肾脏、心脏和消化道。这种器官质量的精确量化将允许在组织-器官水平上更精确地表征适应性产热。此外，体内磁共振波谱法对肝脏脂肪的可用性将允许对“无脂肪肝块”进行量化。这是保证准确定量代谢活跃的肝脏质量的关键。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。拟议的分析将回答许多肥胖和衰老研究人员提出的一个问题——减肥后，在新的体重平衡下，不同的器官和组织对能量消耗的变化有什么贡献？目前的研究将为减少氧化损伤延长寿命的主要机制之一做出独特的重要贡献。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维持体重减轻和延长寿命的干预措施和策略。

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.