Oral glucose tolerance test after 22 weeks of HF feeding.

<p>HFpu and HFs mice were fasted for 5 hours at the start of the light phase, after which mice received glucose via oral gavage. Blood glucose levels were measured before glucose administration and during the 2 hours thereafter (A), and were expressed as iAUC (B).</p

Data_Sheet_4_A Constraint-Based Model Analysis of Enterocyte Mitochondrial Adaptation to Dietary Interventions of Lipid Type and Lipid Load.XLSX

<p>Computational modeling 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.</p

Data_Sheet_2_A Constraint-Based Model Analysis of Enterocyte Mitochondrial Adaptation to Dietary Interventions of Lipid Type and Lipid Load.xlsx

<p>Computational modeling 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.</p

Data_Sheet_1_A Constraint-Based Model Analysis of Enterocyte Mitochondrial Adaptation to Dietary Interventions of Lipid Type and Lipid Load.XLSX

<p>Computational modeling 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.</p

Body weight and total adiposity during 27 weeks of HF feeding.

<p>Body weight (solid lines) and total adiposity (dotted lines) were determined on a weekly basis during the 27 weeks of HFpu and HFs feeding. Total adiposity is expressed as the percentage of total body fat over body weight.</p

Mean adipocyte size and prevalence of crown-like structures in eWAT after 27 weeks of HF feeding.

<p>Representative images (A) of the haematoxylin stainings that were used to determine the average adipocyte surface area (B) in eWAT of HFpu and HFs mice. The bar in each picture represents a distance of 100 μm. The number of CLS (C) was determined with a MAC-2 macrophage staining in eWAT. * P< 0.05 HFs mice vs. HFpu mice.</p

Data_Sheet_3_A Constraint-Based Model Analysis of Enterocyte Mitochondrial Adaptation to Dietary Interventions of Lipid Type and Lipid Load.XLSX

<p>Computational modeling 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.</p

Diet composition of HFpu and HFs.

<p>Diet composition of HFpu and HFs.</p

Indirect calorimetry measurements of HFpu and HFs mice in week 5 and week 20.

<p>Data are expressed as mean ± SEM (n = 11 for HFpu and n = 12 for HFs). Indirect calorimetry measurements during normal, free-feeding conditions were performed after 5 and after 20 weeks of feeding the HFpu or HFs diet. Data were recorded and averaged over 24 hours. Feed intake (FI) and physical activity are also expressed as the percentage in the dark phase (DP) to give insight into the diurnal pattern.</p><p>§ indicates a significant effect of time (§§ <i>P</i><0.01, §§§ <i>P</i><0.001 and §§§§ <i>P</i><0.0001).</p><p>Ŧ indicates a significant effect of the diet (ŦŦ <i>P</i><0.01).</p><p>n.s. non-significant.</p><p>Indirect calorimetry measurements of HFpu and HFs mice in week 5 and week 20.</p

RER during the OxR challenge after 25 weeks of HF feeding.

<p>HFpu and HFs mice were fasted and exposed to normoxic air (A; 20.8% O₂) or to oxygen restriction (B; 12.0% O₂) for 6 hours. Asterisks (in B) indicate the individual time points at which the 2-way ANOVA post-hoc analysis revealed significant differences between HFpu and HFs mice. RER values of individual mice were averaged during the 6 hours in normal or hypoxic air (C) and used to estimate the percentage of energy (en%) from glucose oxidation (D). Blood glucose was measured directly after the exposure to OxR or normal air (E). * <i>P</i><0.05 and ** <i>P</i>< 0.01 HFs mice vs. HFpu mice.</p