Lipoprotein Profiles in Chronic Alcoholics: Use of High-Density Lipoprotein Subspecies Levels to Differentiate Subpopulations

Abstract

Recent research in lipoprotein metabolism has revealed new important contributions of the liver to lipoprotein synthesis and metabolism in addition to its established role in triglyceride and very low-density lipoprotein (VLDL) formation. Examples of these contributions include: (i) the synthesis of apoproteins, which are constituents of lipoproteins and are essential co-factors in the activation of key enzymes involved in lipoprotein metabolism; (ii) synthesis and secretion of lecithin:cholesterol acyltransferase (LCAT), which is responsible, in man, for virtually all plasma cholesterol esterification; (iii) uptake and degradation of chylomil cron remnants, low-density lipoproteins (LDL) and high-density lipoproteins (HDL), and (iv) regulation of cholesterol homeostasis by synthesis of bile acids from cholesterol and excretion of cholesterol in bile. The importance of these hepatic contributions to lipoprotein metabolism is dramatically demonstrated by the profound derangements in lipoprotein concentration and composition which occur as a consequence of hepatocellular (1) or cholestatic (2) liver disease. These changes are largely secondary to abnormalities in lipoprotein synthetic and catabolic functions of the liver.Recent studies of patients with alcoholic hepatitis (3-9) provide evidence that hepatocellular injury is associated with the following alterations in plasma lipoprotein composition: (i) VLDL is relatively normal in lipid composition but deficient in apoproteins E and C; (ii) LDL contains mainly apoprotein (apo) B but is heterogeneous in size and enriched in triglyceride and deficient in esterified cholesterol, and (iii) HDL that is diminished in concentration, enriched in apo E and phospholipid, and deficient in apo A-I and esterified cholesterol. Using density gradient ultracentrifugal techniques, the abnormal HDL has been resolved into discoidal (apo E-rich) and spherical particles (apo A-I rich). Several studies (1, 10) documented low plasma LCAT activity in alcoholic liver disease associated with impaired cholesterol esterification. LCAT deficiency also occurs in nonalcoholic hepatocellular injury. Associated with LCAT deficiency is decreased plasma apo A-I, an activator of LCAT. The catabolism of apo A-I is increased in alcoholic hepatitis, providing a rationale for reduced plasma levels (11).