Fatty acids metabolism in mammalian hepatocytes

FA_1_ruModel of fatty acids metabolism in hepatocytes is developed in the framework of Etherpaths project (FP7) - Characterization and modelling of dietary effects mediated by gut microbiota on lipid metabolism, which is focused on the systems biology of lipid nutrition. It is known that liver is a key player in a lipid metabolism. That is why the modeling of lipids interconversion in hepatocytes is a necessary stage of the Etherpaths project development and a link between models of central carbon metabolism and systemic lipid metabolism in the whole organism, which are also constructed in the framework of this project.

What is the fate of lipids consumed? In intestine lipids are divided into glycerine and fatty acids (FA) by the pancreatic enzymes. FA are consumed by enterocytes to form chylomicrones (ChM – lipoprotein globules with polar external layer and nonpolar lipids inside). Enterocytes release ChM to the lymph, where they are transported into blood. During blood circulation a part of FA from ChM are consumed by tissues (mainly by adipose and muscles). ChM remnants are consumed by liver cells where different length FAs are transformed to C16-C18 FAs. They are further packed into very low dense lipoproteins (VLDL) which are released to the circulation to be transported to the tissues.

On this stage of our work developed model describes the metabolism of three FA (palmitate, stearate and alpha-linolenate) in hepatocyte and formation of triglycerides, phospholipids and cholesterol as parts of VLDL-particle. The model includes the processes of FA beta-oxidation, de novo synthesis and elongation. Model parameters were defined according to literature experimental data. Further we are going to verificate the model with experimental data obtained by our partners of the Etherpath project, to extrapolate the model to other FAs and to link it up to the model central carbon metabolism. At the last stage of the project full model will be integrated to the systemic model of lipid metabolism of the whole organism.

 

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