A model for regulated fatty acid metabolism in liver; equilibria and their changes

Abstract

We build a model for the hepatic fatty acid metabolism and its metabolic and genetic regulations. The model has two functioning modes: synthesis and oxidation of fatty acids. We provide a sufficient condition (the strong lipolytic condition) for the uniqueness of its equilibrium. Under this condition, modifications of the glucose input produce equilibrium shifts, which are gradual changes from one functioning mode to the other. We also discuss the concentration variations of various metabolites during equilibrium shifts. The model can explain a certain amount of experimental observations, assess the role of poly-unsaturated fatty acids in genetic regulation, and predict the behavior of mutants. The analysis of the model is based on block elimination of variables and uses a modular decomposition of the system dictated by mathematical global univalence conditions.