Multi-scale, whole-system models of liver metabolic adaptation to fat and sugar in non-alcoholic fatty liver disease

Insulin sensitivity and verification of sugar consumption in vitro and in silico. a Immunoblot analyses of pAKT/AKT expression (both ~60？kDa) in HepG2 cells stimulated with insulin (n？=？3–4), analysed by one-way ANOVA with Dunnett’s test post hoc between doses and vehicle. b The change in monosaccharide concentration of culture medium in vitro over the first and second 24？h period after treatments of glucose or fructose with (+) and without (？) 100？nM insulin (n？=？4–5), analysed within timepoints between treatment by one-way ANOVA with Tukey’s test post hoc. c–f The objective function was set as either the glucose or fructose transport flux between the external space (medium) and sinusoid space. Maximisation was the uptake of monosaccharide, and minimisation was the production and export into the medium (external space). c Model predictions of glucose concentration in the medium with (+) or without (？) the presence of 100？nM insulin over time alongside experimental data from HepG2 cells (n？=？3–5). d Predicted glucose transport rate over time. e Predictions of fructose concentration over time alongside experimental data from HepG2 cells (n？=？3–5). f Predicted fructose transport rate over time. Data shown as mean？±？SEM. Statistical differences are indicated as * P？<？0.05, ** P？<？0.01, *** P？<？0.001, and **** P？<？0.000