Systems-level computational modeling demonstrates fuel selection switching in high capacity running and low capacity running rats
Fig 4
Simulation of HCR and minimal simulation of LCR rat exercise data.
HCR (blue circles) and LCR (red circles) rat data were collected previously [30] during a graded treadmill experiment. Major pathways (87 reactions) of glucose, FA transport, oxidation, and bioenergetics (Fig 1) were simulated using an ordinary differential equation system (98 state variables). Enzyme activities (X, Eq 4) were adjusted to fit the HCR data (blue circles), while a change in HCR enzyme activities were used to fit the LCR data (red circles). Simulations are represented by lines for HCR (blue) and LCR (red). LCR: solid lines were simulated by decreasing HCR total mitochondrial and FAO activities (error function value = 2.68), red dash-dot lines were simulated by decreasing total HCR mitochondrial enzyme activities only (error function value = 2.89), and dashed lines were simulated by decreasing HCR FAO enzyme activities only (error function value = 4.03). Total acyl-carnitine concentrations shown in panels (E-J) were derived from HCR and LCR gastrocnemius muscle [30]. Error bars represent standard error of the mean, while error bars in panel D were calculated from the propagation of error using errors in JCO2 and JO2 fluxes shown in panel A and B, respectively. (A) HCR and LCR rat carbon dioxide flux (JCO2). (B) HCR and LCR rat molecular oxygen flux (JO2). (C) Plasma lactate from HCR and LCR. (D) Respiratory quotient (JCO2/JO2) for HCR and LCR. (E) Total C16-carnitine muscle concentration for HCR and LCR rats. (F) Total C14-carnitine muscle concentration for HCR and LCR rats. (G) Total C8-carnitine muscle concentration for HCR and LCR rats. (H) Total C4-carnitine muscle concentration for HCR and LCR rats. (I) Total Acetyl-carnitine muscle concentration for HCR and LCR. (J) Total Carnitine muscle concentration for HCR and LCR rats.