Abstract
Several methods have been employed to measure the production of ketone bodies by the liver cells from precursors, such as free fatty acids. This study quantifies the kinetics of oleate (a free fatty acid) and the relative production of ketone bodies (acetoacetate arxi 3-hydroxybutyrate) by using a mathematical model. Experimental data were collected from perfusion experiments carried out in isolated rat hepatocytes. The model describes the dynamic behaviour of the three compounds in the perfusion medium in the presence of increasing doses (0.25, 0.50 and 1.00 mM) of oleic acid. It accounts for the disappearance of oleic acid by considering the conversion to ketone bodies and the degradation to other metabolic pathways. Because of identifiability problems the two ketone bodies could not be analyzed separately, thus their ratio has been considered. With the highest dose (1 mM), the fractional conversion of oleate to ketone bodies decreased raising the hypothesis of a saturative mechanism for the liver production of ketone bodies. This hypothesis was also supported by the unchanged degradation of oleate to other metabolic pathways, despite the marked change in the dose. In conclusion, this model allows inferences in the liver physiology of free fatty acids and ketone bodies without the need of radioactive tracers.
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