A Mathematical Model Connecting Appetite-Driven Food Intake to Metabolic Changes across Diet and GLP-1RA Treatments in Mice

Mouse models are widely used to study obesity and the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on appetite-driven meal responses and eating behaviours. However, connecting these behavioural changes to disease prevention remains limited. One reason is that eating behaviour is often summarised as daily or weekly energy intake, obscuring meal-level dynamics. Here we present a mathematical model of mouse appetite-driven food intake across diets and treatment with the GLP-1RAs semaglutide and exenatide. The model jointly described three studies and passed both qualitative assessments and a statistical {chi}2 test (disagreement<threshold, 348<1111). Predictive performance was subsequently validated using four pre-existing studies and one new study. Finally, the model was used to simulate mouse populations under dietary and GLP-1RA interventions, with predictions showing qualitative agreement with the literature. This work aids preclinical drug discovery, supports mouse study design, and improves understanding of how individual meals accumulate into long-term physiological changes.