Table 1.

Comparison of observed biological patterns to model output. Abbr.: FA – fatty acid, GPx – glutathione peroxidase, HFD – high-fat diet, H₂O₂ – hydrogen peroxide, IR – ischemia/reperfusion, LPO – lipid peroxidation, MDA – malondialdehyde, O₂ – oxygen, TBARS – Thiobarbituric acid reactive substances, TG – triglyceride.

Validation issue	Model simulation	Experimental observation
Intracellular O2 concentration (normoxia)	Range of intracellular O2 concentrations during normoxic simulations is between 0.22 mM–0.27 mMa	Physiological O2 concentration is up to 250 μM (0.25 mM) [68]
Modifying FA uptake rate	Enhancing the rate of FA uptake (via increased value of parameter kFAup) raised hepatic TG content up to ~200%, TG synthesis and TG export up to ~120%	CD36 overexpression enhances the rate of FA uptake, which increases hepatic TG content to ~190%, TG synthesis to ~130% and TG export to ~120% (compared to control) [69]
Modifying mitochondrial FA oxidation	Decreasing the rate of FA oxidation (via decreasing the parameter value koxid) causes an increased accumulation of TG	Inhibition of mitochondrial oxidation by tetracycline increases hepatic TG content [70]
Effect of a HFD	Strong increase of the intracellular FA concentration from low to high plasma FA supply (between ~ 300% to ~500%a); increase of H2O2 production from low to high plasma FA supply (between ~140% to ~170%a); increase of GPx activity (between ~120% to ~175%a) and MDA concentration (between ~170% to 300%a) from low to high plasma FA supply	~300% increase of intracellular FA concentration under a HFD in Wistar rats (compared to control diet) [71]; ~145% increase of H2O2 production under a HFD in Swiss mice (compared to control diet) [72]; GPx activity increases by ~195% and MDA content increases by ~150% under a HFD in rabbits (compared to control diet) [73]
Effect of hypoxia on H2O2 generation & hepatic FA & TG content	H2O2 production rate increases up to 200% of the normoxic value under hypoxia with moderate plasma FA supply; accumulation of intracellular FAs and TGs under hypoxia (see Fig. 6A, B)	H2O2 generation increases up to ~190% of control over 72 h of hypoxia [74]; Increased hepatic concentration of FAs and TGs under hypoxia [75]
LPO under HFD after IR	MDA concentration strongly increases after hypoxia & reoxygenation (2. stable state) under steatotic conditions	Level of TBARS strongly increases under a HFD compared to a standard diet after IR [76], similar observation directly for the MDA concentration [77]

^aResults depend on the plasma FA concentration (parameter [FA]_blood) chosen to represent the control and HFD, respectively.