COMPUTER MODEL OF HUMAN SUBSTRATE METABOLISM

在自由生活的个体中，每日食物摄入量的变化相当大，并且与能量消耗(EE)的变化不太同步。虽然这会导致严重的短期能源失衡，但能源平衡的长期误差通常非常小(例如，一年内能源周转量的1%至2%)。由于食物摄入量引起的EE变化仅略微减弱了饮食过量或饮食不足的影响，因此体重维持主要取决于食物摄入量对EE的适当调整。人体的糖原储备并不比一天习惯性摄入的碳水化合物(CHO)多多少。因此，进化被迫开发出特别优先于维持CHO平衡的调节功能。在不受食物限制的情况下理解体重调节的一个重要问题是，维持稳定的糖原储备是仅仅通过调节葡萄糖氧化到CHO摄入量，还是通过改变糖原水平对食物摄入量的影响来帮助维持稳定的糖原储备。然而，鉴于对每日能量摄入量和平衡的松散控制，很难确定这一机制和/或其他机制是否参与了对食物摄入量的适当“纠正变化”。为了对这些困难有一些了解，开发了一个人体能量代谢的计算机模型。它使用系统动力学方法，在这种方法中，在连续的时间间隔内计算不同舱室内容物的变化。事件的进程可以在表格和图形中显示为时间的函数、几个小时或数百天。当条件保持不变时，模拟会在时间上引导到稳定状态；如果达到异常配置，他们会建议需要在模型中实施的更改，使其逐渐与目前人类底物新陈代谢的知识更一致。这项赠款申请寻求资金，以开发目前的计算机模型，特别是通过整合反映人体主要器官底物代谢的子系统来构建该模型。随着时间的推移，将开发一个用户友好的界面，使研究人员、学生、营养学家、营养学家和其他人有一个互动的机会，以获得人体底物新陈代谢的图像，并观察其对用户可以指定的条件的反应，包括体重变化。

Variations in daily food intake are quite large in free-living individuals and not well synchronized with variations in energy expenditure (EE). Although this leads to substantial short-term energy imbalances, long-term errors in the energy balance are generally remarkably small (e.g. <1 to 2% of energy turnover over a year). Because changes in EE elicited by food intake attenuate only slightly the impact of over- or under-eating, weight maintenance depends primarily on appropriate adjustment of food intake to EE. The body's glycogen reserves are not much greater than the amount of carbohydrate (CHO) habitually consumed in one day. Evolution was therefore compelled to develop regulatory features giving specially high priority to the maintenance of CHO balance. An important issue in understanding body weight regulation when access to food is unrestricted, is whether maintenance of stable glycogen reserves is achieved merely through adjustment of glucose oxidation to CHO intake, or whether this may be helped by influences induced by changing glycogen levels on food intake. However, given the loose control of daily energy intake and balance, it is difficult to establish whether this, and/or other mechanisms are involved in bringing about appropriate "corrective changes" beta in food intake. To gain some insight about these difficulties, the development of a computer model of human energy metabolism was undertaken. It uses the Systems Dynamics approach in which changes in the content of various compartments are computed over consecutive time intervals. The course of events can be displayed in tables and graphs as a function of time, over hours, or hundreds of days. When conditions are kept constant, the simulations lead in time to steady-states; if aberrant configurations are reached, they suggest the changes which need to be implemented in the model to make it progressively more consistent with current knowledge of substrate metabolism in man. This grant application seeks funds to pursue the development of the current computer model, notably to construct it by integration of subsystems reflecting substrate metabolism in the body's major organs. In time, a user-friendly interface will be developed enabling investigators, students, dieticians, nutritionists and others to have an interactive opportunity to obtain an image of substrate metabolism in man and to observe its responses, including body weight changes, to conditions which can be specified by the user.