A whole-body multi-scale mathematical model for dynamic simulation of the metabolism in man

TL;DR

This paper introduces a comprehensive multi-scale mathematical model of human metabolism, integrating organ-specific reactions, hormonal regulation, and feeding cycles to simulate metabolic dynamics over several days.

Contribution

It presents a systematic, compact modeling approach for whole-body metabolism, incorporating hormonal regulation and storage forms, enabling realistic simulation of metabolic responses.

Findings

Model includes 7 organs, 16 metabolites, 31 enzymatic reactions.

Simulates feed-fast metabolic cycles over multiple days.

Can be used for virtual clinical trials and treatment strategy development.

Abstract

We propose a whole-body model of the metabolism in man as well as a generalized approach for modeling metabolic networks. Using this approach, we are able to write a large metabolic network in a systematic and compact way. We demonstrate the approach using a whole-body model of the metabolism of the three macronutrients, carbohydrates, proteins and lipids. The model contains 7 organs, 16 metabolites and 31 enzymatic reactions. All reaction rates are described by Michaelis-Menten kinetics with an addition of a hormonal regulator based on the two hormones insulin and glucagon. We incorporate ingestion of food in order to simulate metabolite concentrations during the feed-fast cycle. The model can simulate several days due to the inclusion of storage forms (glycogen, muscle protein and lipid droplets), that can be depleted if food is not ingested regularly. A physiological model incorporating complex cellular metabolism and whole-body mass dynamics can be used in virtual clinical trials. Such trials can be used to improve the development of medicine, treatment strategies such as control algorithms, and increase the likelihood of a successful clinical trial.