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The iron disposition regulates liver homeostasis of cholesterol and bile acids
 Prašnická, Alena ; Mičuda, Stanislav (advisor) ; Pejchal, Jaroslav (referee) ; Večeřa, Rostislav (referee)
Changes in the iron content are among the most common metabolic diseases with a number of possible pathophysiological consequences for various body functions. The phenomenon accompanying these situations is the change in cholesterol homeostasis with possible extension to bile acids (BA), ie major executive and regulatory molecules in the metabolism of endobiotics, what can play an important role in associated organ dysfunctions. Since there was only a minimal amount of information in this area, the aim of this work was to evaluate the effect of iron overload and deficiency on the processes involved in BA turnover with the identification of involved molecular mechanisms. The first assessed field was the evaluation of iron deficiency (ID) using a suitable rat model, where ID was induced by a specific diet. This has demonstrated a significant inducing effect on both classical and alternative pathways for BA synthesis from cholesterol. Together with the induction of cholesterol biliary secretion in ID group it led to statistically significant decrease of plasma cholesterol concentrations. The subsequent BA-dependent choleretic effect was induced by their increased liver disposition, without affecting the expression of corresponding transporters, as verified by the kinetic study with 3 H-taurocholate....
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