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: 9032839
• 负责人: WEI SHEN
• 金额: $ 16.39万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9032839
• 关键词: Contribution; Organ; Size; Adaptive; Thermogenesis

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）：适应性产热定义为在热量限制的情况下，静息能量消耗（REE）的降低超过基于体重和组成变化的预期。适应性产热的准确定量需要对异质体组成成分进行精确测量。最常用的模型，旨在预测REE组的身体成分，脂肪质量和脂肪的质量（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。大多数以前的减肥研究，研究了适应性产热使用FFM预测的能量消耗。迄今为止，只有一项研究检查了短期体重减轻中的器官大小变化（即，3个月）;目前尚不清楚在长期热量限制和体重稳定的条件下是否仍存在适应性产热。使用CALERIE数据集，有可能首次评估长期热量限制期间的适应性产热，在第1年）和在重量稳定条件下（即，第二年）。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。这种器官质量的准确定量将允许在组织器官水平上更精确地表征适应性产热。此外，通过体内磁共振波谱法获得的肝脏脂肪的可用性将允许量化“无脂肪肝脏质量”。这对于保证代谢活性肝质量的准确定量至关重要。这项研究将首次将长期热量限制下的适应性产热的细胞水平证据与组织器官水平证据结合起来。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-在减肥后的新体重平衡中，不同器官和组织对能量消耗变化的贡献是什么。本研究将独特地为增加寿命并减少氧化损伤的主要拟议机制之一做出重要贡献。所获得的知识将为未来的研究铺平道路，以准确地评估适应性产热机制的器官和组织的大小无关。这些收集的知识将有助于制定干预措施和策略，以维持减肥和延长寿命。