A Constraint-Based Model Analysis of Enterocyte Mitochondrial Adaptation to Dietary Interventions of Lipid Type and Lipid Load

Computational modelling of mitochondrial adaptability and flexibility in the small intestine upon different nutritional exposures will provide insights that will help to define healthy diet interventions. Therefore, a murine enterocyte-specific mitochondrial constraint-based metabolic model (named MT_mmuENT127) was constructed and used to simulate mitochondrial behavior under different dietary conditions, representing various levels and composition of nutrients absorbed by the enterocytes in mice, primarily focusing on metabolic pathways. Our simulations predicted that increasing the fraction of marine fatty acids in the diet, or increasing the dietary lipid/carbohydrate ratio resulted in (i) an increase in mitochondrial fatty acid beta oxidation, and (ii) changes in only a limited subset of mitochondrial reactions, which appeared to be independent of gene expression regulation. Moreover, transcript levels of mitochondrial proteins suggested unaltered fusion-fission dynamics by an increased lipid/carbohydrates ratio or by increased fractions of marine fatty acids. In conclusion, our enterocytic mitochondrial constraint-based model was shown to be a suitable platform to investigate effects of dietary interventions on mitochondrial adaptation and provided novel and deeper insights in mitochondrial metabolism and regulation.