CHOLESTERYL ESTER TRANSFER ACTIVITY IN LIVER-DISEASE AND CHOLESTASIS,AND ITS RELATION WITH FATTY-ACID COMPOSITION OF LIPOPROTEIN LIPIDS

Liver disease is accompanied by major qualitative and quantitative dis turbances in plasma lipoprotein metabolism, the extent and intensity o f which depend on the degree of parenchymal damage, cholestasis, or bo th. The main objective of this study was to determine the cholesteryl ester transfer CETP activity and its association with the lipoprotein neutral lipid composition in patients with either liver cirrhosis or c holestasis, as compared to normal controls. Lipoproteins were isolated by ultracentrifugation, lipids and apolipoproteins were measured by c onventional methods, and the fatty acid composition was established by gas chromotography; CETP activity in lipoprotein-deficient plasma was measured by determining the transfer of [H-3]cholesteryl esters from HDL to VLDL, Lipoprotein lipase and hepatic lipase activities were mea sured in post-heparin plasma by radiochemical methods. In patients wit h liver cirrhosis, low levels of VLDL, HDL, apo B, and Lp(a) were obse rved, as well as a change in the composition of HDL particles, with in creases in the relative proportion of triglyceride and free cholestero l. Respectively, the last two changes could be attributed in part to t he low hepatic lipase activity observed in this study, and to the low lecithin:cholesterol acyltransferase activity previously observed by o thers. In patients with cholestasis, a moderate hyperlipidemia due to the elevation of LDL was found. In contrast, HDL and apo A-I levels we re very low reflecting a low number of HDL particles, which also had a ltered compositions with increases in the triglyceride and free choles terol contents relative to apo A-I and esterified cholesterol, respect ively. As regards the fatty acid composition of lipoprotein lipids, th e two groups of patients showed, in general, a lower proportion of lin oleic acid and a compensating higher proportion of oleic acid as compa red to the controls, changes that were observed in both cholesteryl es ters and triglycerides. In contrast, the proportions of oleic and palm itoleic acids in phospholipids were increased, whereas that of stearic acid was decreased in patients as compared to controls. In patients w ith liver cirrhosis, as well as in controls, no changes were observed in the fatty acid compositions of cholesteryl ester, triglycerides, or phospholipids among the different lipoproteins, which probably reflec ts the equilibration reached by the action of CETP. In patients with c holestasis, no differences were observed in fatty acid composition amo ng the lipoprotein phospholipids but, interestingly, cholesteryl ester s from VLDL had a significantly lower linoleic acid content than those from HDL, whereas triglycerides from VLDL had significantly higher ol eic acid and lower linoleic acid contents than those from HDL. This di stinct fatty acid composition of the neutral lipids between lipoprotei ns was associated with a significant decrease (25%) in the cholesteryl ester transfer activity in patients with cholestasis. We suggest that fat malabsorption due to the biliary defect may induce a decrease in cholesteryl ester transfer protein synthesis or secretion, which in tu rn would slow the equilibration of the neutral lipids among plasma lip oproteins.