Implementing the Digital Twin concept in toxicology: modeling hepatic metabolic fluxes and the dynamics of their modulation during exposure to food contaminants

Summary :

Many chemical compounds present in human diets are strongly suspected of being metabolic disruptors, capable of inducing metabolic modulations that very likely contribute to the development of pathologies such as obesity, type II diabetes and hepatic steatosis. The aim of this thesis project will be to develop an in silico model of the hepatic metabolic network in order to explore the metabolic effects induced by exposure to food contaminants (FC), focusing on the analysis of the establishment dynamics of metabolic perturbations and their interaction with diet. This project will draw on systems modeling approaches, in particular dedicated constrained modeling approaches to the analysis of fluxes in metabolic networks, and kinetic exometabolomics data. It will be at the center of the original approach developed as part of the HepatO'twin project, based on the concept of the Digital Twin. The model developed should provide clues as to whether and how modulations of hepatic metabolism induced by exposure to a FC are likely to prevent an adapted metabolic response in a situation of nutritional stress, such as lipid and/or carbohydrate overloads as observed in so-called

Contact :

• Koloina Rabemanantsoa
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