Lecithin:Cholesterol Acyltransferase Deficiency and Cell Membrane Lipids and Function in Human Liver Disease

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Abstract
There are several lipoprotein abnormalities in human liver disease, many of which can be related to a reduced LC AT activity. Exchange is known to occur between the lipids of the plasma lipoproteins and their counterparts in the membranes of erythrocytes and other cells. There have been few studies on the effect of this exchange on cell lipid composition and function in liver disease. In agreement with other workers we found erythrocyte lipid composition to be altered in both parenchymal liver disease and obstructive jaundice with increases in cholesterol and lecithin concentrations and raised cholesterol: phospholipid molar ratio (C/P). Plasma LCAT activity showed significant inverse correlations with these erythrocyte lipid changes in parenchymal liver disease but not in obstructive jaundice. Increase in membrane C/P ratio is associated with decreased membrane fluidity, and in erythrocytes from patients we have demonstrated the C/P ratio to be related to an abnormal permeability to sodium and to an enhanced ability of the cells to fuse in vitro in the presence of a chemical fusogen. The plasma membrane lipid composition of other cells may also be altered in liver disease. We found platelet C/P ratio was increased and correlated with erythrocyte C/P ratio. The proportion of lecithin in platelets increased and that of sphingomyelin and phosphatidylethanolamine decreased. Cultured human skin fibroblasts also had an increased C/P ratio when lipoproteins from patients were added to their culture media. The largest increases occurred in patients with the lowest LCAT activity. These observations suggest that alterations in plasma membrane lipids, in part as a consequence of LCAT deficiency, may underlie some of the cellular disturbances and metabolic abnormalities in liver disease.