Relating tissue/organ energy expenditure to metabolic fluxes in mouse and human: experimental data integrated with mathematical modeling.
Relating tissue/organ energy expenditure to metabolic fluxes in mouse and human: experimental data integrated with mathematical modeling.
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DOI：
10.14814/phy2.12159
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发表时间：
2014-09-01
影响因子：
2.5
通讯作者：
Lai N
中科院分区：
文献类型：
--
作者：
Kummitha CM;Kalhan SC;Saidel GM;Lai N
人类疾病的小鼠模型用于研究导致全身能量消耗（EE）改变的代谢和生理过程，这是所有身体器官和组织的EE总和。同位素技术、基质的动静脉差异、氧气和血流测量可提供量化组织/器官EE和基质氧化的基本信息。为了补充和整合实验数据，定量数学模型分析已应用于实验设计和代谢通量的评估。在这项研究中，提出了一种方法来量化的主要器官的能量消耗代谢通量测量。使用基于质量和能量平衡的数学模型量化小鼠组织/器官系统和全身中能量代谢的主要代谢途径的代谢通量和底物利用。该模型由六个器官/组织隔室组成：脑、心脏、肝脏、胃肠道、肌肉和脂肪组织。每个组织/器官都用不同的代谢反应系统来描述。该模型量化了小鼠在过夜禁食条件下的代谢和能量特征。代谢物的稳态质量平衡以及碳水化合物和脂肪的能量平衡与可用的实验数据相结合，以计算每个组织/器官中的代谢通量、底物利用率和耗氧量。该模型作为设计实验的范例，具有量化组织/器官通量所需的最小可靠测量值，并量化组织/器官EE对全身EE的贡献，目前无法轻松确定。e12159该模型将代谢通量测量与组织器官系统和全身的能量消耗相关联。该模型可用于设计实验，方法是选择最小可靠的组织/器官通量测量值，以量化组织/器官对全身能量消耗的贡献，而这是当前实验方法无法轻易获得的。
Mouse models of human diseases are used to study the metabolic and physiological processes leading to altered whole‐body energy expenditure (EE), which is the sum of EE of all body organs and tissues. Isotopic techniques, arterio‐venous difference of substrates, oxygen, and blood flow measurements can provide essential information to quantify tissue/organ EE and substrate oxidation. To complement and integrate experimental data, quantitative mathematical model analyses have been applied in the design of experiments and evaluation of metabolic fluxes. In this study, a method is presented to quantify the energy expenditure of the main mouse organs using metabolic flux measurements. The metabolic fluxes and substrate utilization of the main metabolic pathways of energy metabolism in the mouse tissue/organ systems and the whole body are quantified using a mathematical model based on mass and energy balances. The model is composed of six organ/tissue compartments: brain, heart, liver, gastrointestinal tract, muscle, and adipose tissue. Each tissue/organ is described with a distinct system of metabolic reactions. This model quantifies metabolic and energetic characteristics of mice under overnight fasting conditions. The steady‐state mass balances of metabolites and energy balances of carbohydrate and fat are integrated with available experimental data to calculate metabolic fluxes, substrate utilization, and oxygen consumption in each tissue/organ. The model serves as a paradigm for designing experiments with the minimal reliable measurements necessary to quantify tissue/organs fluxes and to quantify the contributions of tissue/organ EE to whole‐body EE that cannot be easily determined currently. e12159 The model relates metabolic flux measurements to the energy expenditure in tissue–organ systems and whole body. The model can be used in designing experiments by selecting the minimal reliable tissue/organs flux measurements necessary to quantify the contributions of tissue/organ to whole‐body energy expenditure that cannot be easily obtained with the current experimental methodologies.