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Mathematical modeling of cholesterol homeostasis 59

• the regulation of CETP activity, and
• the change in tissue requirements for cholesterol with age.
The two-compartment mathematical model developed in this study showed
a significant contribution of bile in the maintenance of cholesterol homeo-
stasis (Hrydziuszko et al., 2015). Further studies with respect to the exten-
sion of the model to include a third compartment representing the
gallbladder are highly warranted. The expected response to a meal contain-
ing fat and cholesterol is contraction of the gallbladder and release of bile
carrying some cholesterol into the duodenum—in terms of the model, it
means that in addition to the constant component m out , the variable
*
component M out should be considered. Thus, some cholesterol enters the
intestine from the bile and the gallbladder is filled with the new hepatic bile,
which again carries cholesterol from the liver. When the gallbladder is full, a
constant flow (m out ) of the hepatic bile can be expected. Extending the
model by a third compartment also creates the possibility of studying the
effect of the primary component of the bile, that is, cholic acid on cholesterol
homeostasis, because it is synthesized in the liver from cholesterol molecules.
A well-defined three-compartment model could open the possibility of test-
ing the susceptibility to the formation of gallstones. In addition, it will enable
analyzing the effect of the dysfunction of gallbladder motility and condition
of the bile ducts on cholesterol homeostasis.

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