Analysis of Hepatic Lipid Metabolism Model: Simulation and Non-Stationary Global Sensitivity Analysis

Abstract

Lipid metabolism is a complex process and it is extremely helpful to simulate its performance with different models that explain all the biological processes that comprise it, which then enables its better understanding as well as understanding the kinetics of the process itself. Typically, kinetic parameters are obtained from a number of sources under specific experimental conditions, and they are a source of uncertainty. Sensitivity analysis is a useful technique for controlling the uncertainty of model parameters. It evaluates a model's dependence on its input variables. In this work, hepatic lipid metabolism was mathematically simulated and analyzed. Simulations of the model were performed using different initial plasma glucose (GB) and plasma triacylglyceride (TAG) concentrations according to proposed menus for different meals (breakfast, lunch, snack and dinner). A non-stationary Fourier amplitude sensitivity test (FAST) was applied to analyze the effect of 78 kinetic parameters on 24 metabolite concentrations and 45 reaction rates of the biological part of the hepatic lipid metabolism model at five time points (tf = 10, 50, 100, 250 and 500 min). This study examined the total influence of input parameter uncertainty on the variance of metabolic model predictions. The majority of the propagated uncertainty is due to the interactions of numerous factors rather than being linear from one parameter to one result. Obtained results showed differences in the model control regarding the different initial concentrations and also the changes in the model control over time. The aforementioned knowledge enables dietitians and physicians, working with patients who need to regulate fat metabolism due to illness and/or excessive body mass, to better understand the problem.