Effect of chronic alcohol ingestion on the binding of high density lipoproteins to rat hepatic membranes: involvement of apolipoprotein E.

Feeding alcohol to rats produces high density lipoproteins (HDL) particles that exhibit lowered apolipoprotein (apo) E:apo A1 ratio. In this study, we have carried out experiments to compare the abilities of apo E-deficient HDL particles of the alcohol-fed rat and apo E-sufficient HDL particles of the control rat to bind to hepatic membranes. When rat hepatic membranes were incubated with rat serum HDL of physiological concentrations (< or = 200 micrograms HDL-apo A1/ml), binding of HDL to hepatic membranes showed concentration dependent on HDL-apo A1. Polyclonal antibodies that specifically recognize apo A1 and apo E inhibited HDL binding to hepatic membrane while the antibody against apo AIV did not. The binding of 125I-apo A1-HDL was diminished by adding excess amount of unlabeled HDL to the incubation mixture. Apo E-deficient serum HDL obtained from alcohol-fed rats competed less efficiently against radiolabeled HDL for binding to rat hepatic membrane than normal HDL from control animals. The defect in apo E-deficient serum HDL obtained from alcohol-fed rats can be corrected by preincubation with added purified apo E. We hypothesize that this weaker binding may result in slower degradation of apo E-deficient HDL particles by the liver and in part explains the higher plasma HDL levels found in alcohol-drinking animals.