6533b7d1fe1ef96bd125be80

RESEARCH PRODUCT

Regulation of the activity of the Cholesteryl Ester Tranfer Protein (CETP) : electrostatics interactions with carboxylic derivatives (Non Esterified Fatty Acids and Retinoids)

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description

In human plasma, the cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism by promoting the net mass transfer of cholesteryl esters from HDL towards apoB-containing lipoproteins, and the transfer of triglycerides from VLDL towards HDL and LDL. Thus CETP arises as a potentially important factor in plasma lipoproteins metabolism, a statement which raised a considerable interest in identifying the factors which may regulate CETP activity.In our in vitro studies, we demonstrated that amphipathic molecules (non esterified fatty acids and retinoic acids) constituted of one carboxylic head group and one hydrophobic carbon chain are able to increase the cholesteryl ester transfer protein activity by increasing the electronegativity of lipoprotein particles.In vivo, our studies revealed a significant correlation between concentration of non esterified fatty acid bound to lipoproteins and the CETP activity in normolipidemic subjects. This role of non esterified fatty acids is increased under pathological conditions such as analbuminemia or nephrotic syndrome associated with a redistribution of plasma non esterified fatty acids from albumin towards lipoproteins.By using an electrophoretic method, we demonstrated that in analbuminemic patients there was a preferential cholesteryl ester transfer towards the most electronegative lipoproteins with the highest non esterified fatty acid content.Taken all together, our results suggest that non esterified fatty acids may play a role in modulating the cholesteryl ester transfer activity and thus influence the atherogenicity of lipoprotein profile.