Estimating the Continuous-Time Dynamics of Energy and Fat Metabolism in Mice
Estimating the Continuous-Time Dynamics of Energy and Fat Metabolism in Mice
复制标题
DOI：
10.1371/journal.pcbi.1000511
复制
发表时间：
2009-09-01
影响因子：
4.3
通讯作者：
Hall, Kevin D.
中科院分区：
文献类型：
--
作者：
Guo, Juen;Hall, Kevin D.
小鼠已成为研究体重调节分子机制的最受欢迎的生物体。但是，要了解分子对体重产生影响的生理背景，需要了解能量摄入、能量消耗和燃料选择。此外，在一个孤立的时间点进行的这些变量的测量不能解释为什么体重具有其当前值，因为体重是由过去的能量和大量营养素不平衡的历史决定的。虽然食物摄入量和体重变化可以在几周内频繁测量（小鼠的相关时间尺度），但相应地频繁测量能量消耗和燃料选择目前是不可行的。为了解决这个问题，我们开发了一种基于能量守恒定律的数学方法，该方法使用测量的体重和食物摄入量的时间过程来估计能量输出和净脂肪氧化的潜在连续时间动态。我们将我们的方法应用于雄性C57 BL/6小鼠，在几周的体重增加和减轻期间食用各种随意饮食，并首次连续时间估计观察到的身体组成变化的能量输出和净脂肪氧化率。我们发现，在饮食转换后的头几天内，短暂的能量和脂肪不平衡可以占总体重变化的很大一部分。我们还发现了一条与雄性C57 BL/6小鼠体内脂肪和无脂肪质量相关的时不变曲线，该曲线的形状决定了饮食、燃料选择和身体成分之间的相互关系。
The mouse has become the most popular organism for investigating molecular mechanisms of body weight regulation. But understanding the physiological context by which a molecule exerts its effect on body weight requires knowledge of energy intake, energy expenditure, and fuel selection. Furthermore, measurements of these variables made at an isolated time point cannot explain why body weight has its present value since body weight is determined by the past history of energy and macronutrient imbalance. While food intake and body weight changes can be frequently measured over several weeks (the relevant time scale for mice), correspondingly frequent measurements of energy expenditure and fuel selection are not currently feasible. To address this issue, we developed a mathematical method based on the law of energy conservation that uses the measured time course of body weight and food intake to estimate the underlying continuous-time dynamics of energy output and net fat oxidation. We applied our methodology to male C57BL/6 mice consuming various ad libitum diets during weight gain and loss over several weeks and present the first continuous-time estimates of energy output and net fat oxidation rates underlying the observed body composition changes. We show that transient energy and fat imbalances in the first several days following a diet switch can account for a significant fraction of the total body weight change. We also discovered a time-invariant curve relating body fat and fat-free masses in male C57BL/6 mice, and the shape of this curve determines how diet, fuel selection, and body composition are interrelated.