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。虽然这会导致大量的短期能量不平衡，但能量平衡中的长期误差通常非常小（例如，低于一年能量周转量的2%）。由于食物摄入引起的情感表达变化只会轻微减弱饮食过量或饮食不足的影响，因此维持体重主要取决于适当调整情感表达的食物摄入。人体的糖原储备并不比一天中习惯消耗的碳水化合物（CHO）多多少。因此，进化被迫发展出特别重视维持CHO平衡的调节特征。当不受限制地获取食物时，理解体重调节的一个重要问题是，维持稳定的糖原储备是否仅仅通过调节葡萄糖氧化到CHO的摄入来实现，或者这是否可能通过改变糖原水平对食物摄入的影响来帮助实现。然而，由于对每日能量摄入和平衡的控制不严格，很难确定这一机制和/或其他机制是否涉及对食物摄入进行适当的“纠正性改变”。为了深入了解这些困难，开发了人体能量代谢的计算机模型。它使用系统动力学方法，在连续的时间间隔内计算各个隔间内容的变化。事件的过程可以在表格和图表中显示为时间的函数，以小时或数百天为单位。当条件保持不变时，模拟在时间上导致稳态；如果达到了异常的结构，他们建议在模型中实施一些改变，使其逐渐与人类底物代谢的当前知识更加一致。这项拨款申请寻求资金，用于发展由子系统集成构建的计算机模型，这些子系统本身是人体主要器官中底物代谢的模型。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、营养师、营养学家和其他人有一个互动的机会来获得人体底物代谢的图像，并观察其对可由用户指定和改变的条件的反应。

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. less than the 2 percent 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 of EE. The body's glycogen reserved are not much greater than the amount of carbohydrate (CHO) habitually consumed in one day. Evolution was therefore compelled to develop regulatory features giving especially high priority to the maintenance of CHO balance. An important issue in understanding body weight regulation, when access to food in 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' 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 a computer model constructed by integration of subsystems which themselves are models of 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 images of substrate metabolism in man and to observe its responses to conditions which can be specified and altered by the user.