Development of compartmental models in stable-isotope experiments: application to lipid metabolism

Kinetic experiments are of great importance in lipid research because they further the understanding of lipid metabolism in vivo and help to explain the physiopathology of lipid disorders in humans. At present, due to species specificity, no valid animal model can efficiently replace a study in humans to explore lipid metabolism, and the use of radioactive tracers is restricted in humans. Thus, stable-isotope tracer kinetic studies have become an important component of research programs to achieve in humans a quantitative understanding of the dynamics of metabolic processes in vivo. The aim of this review is to describe the practical aspects of compartmental model development in stable-isotope experiments. The recent development of computer hardware and modeling software has dramatically facilitated the task of the modeler in his or her calculations. In the current review, we show that the model may be considered an integral component of the experimental design and that model development must obey strict rules to provide a rigorous solution. The main difficulties of model development in tracer experiments, such as experiment design, model identifiability, data expression, comparison of models, or tracer recycling, are presented with extensive references. We have paid particular attention to kinetic modeling in stable-isotope experiments because they have shown the greatest development in recent years.