The studies will utilize human (alcoholic hepatitis) and experimental (galactosamine-treated rats) liver disease to investigate the pathophysiology of the hypertriglyceridemia of acute hepatocellular injury.
The specific aims are: (1) To characterize the apo C-peptide content and the apo C-III isoform distribution in the plasma lipoproteins of patients with alcoholic hepatitis at the onset of illness and throughout their recovery; (2) To characterize the apo E content and isoform distribution in the plasma lipoproteins of patitents with alcoholic hepatitis at the onset of illness and throughout their recovery; (3) To determine whether the TG-rich LDL of liver disease is of hepatic or intestinal origin; (4) To determine lecithin:cholesterol acyltransferase (LCAT) mass and its relationship to LCAT activity and cholesterol esterification rate in patients with alcoholic hepatitis and to correlate these parameters with the composition, quantitation and ultrastructure of the plasma lipoproteins; (5) To determine the activities of lipoprotein lipase and hepatic triglyceride lipase in post-heparin plasma of patients with alcoholic hepatitis and to correlate their activities with plasma lipid levels and the concentration of apo C-II and C-III peptides in the TG-rich lipoproteins; (6) To determine the kinetics of chylomicron clearance in patients with alcoholic hepatitic and to correlate such changes with chylomicron apoprotein composition and quantitation; (7) To determine whether the clearance of chylomicron remnants is defective in patients with alcoholic hepatitis and in rats with galactosamine-induced hepatitis and if so, in rats, to determine whether the defect is at the membrane receptor level; (8) To investigate the synthesis and composition of hepatic lipoproteins by the galactosamine hepatitic liver using isolated liver perfusion. The long-term objective of these studies is to define the normal physiological processes involved in the metabolism of triglyceride-rich lipoproteins and to comprehend derangements of lipoprotein metabolism in liver disease in man.
| Cabana, V G; Siegel, J N; Sabesin, S M (1989) Effects of the acute phase response on the concentration and density distribution of plasma lipids and apolipoproteins. J Lipid Res 30:39-49 |
