Infusion of atherogenic lipoprotein particles increases hepatic lipase activity in the rabbit

Hepatic lipase plays a key role in the turnover of potentially atherogenic lipoprotein remnants and in determining the relative distribution of high density lipoprotein (HDL) particle size subclasses. Rabbits fed a cholesterol-enriched diet have been found to accumulate potentially atherogenic chylomicron remnants and beta-very low density lipoprotein (beta-VLDL) and show a rapid increase in liver and postheparin plasma hepatic lipase activity. To determine whether the particles that accumulate during cholesterol feeding are a stimulus for this increase in hepatic lipase activity, we infused normal chow-fed rabbits with a chylomicron remnant plus beta-VLDL-enriched plasma fraction isolated from rabbits fed 0.5% cholesterol-supplemented chow. The infusion of this plasma fraction for 4 h increased hepatic lipase activity up to 2.9-fold over control rabbits and resulted in a loss of larger sized HDL particles consistent with the action of hepatic lipase. The increase in activity was significantly correlated with the concentration of infusate phospholipid, unesterified cholesterol, and esterified cholesterol, but not with the infusate triglyceride concentration. The change in the plasma cholesterol concentration of recipient rabbits, which reflects the degree of lipoprotein accumulation in these rabbits, was also significantly correlated with the change in hepatic lipase activity. However, a chylomicron remnant and beta-VLDL-depleted fraction of plasma from cholesterol-fed rabbits did not increase hepatic lipase activity. Furthermore, triglyceride presented as an artificial lipid emulsion (Intralipid) was not able to stimulate hepatic lipase activity, although triglyceride is a substrate for hepatic lipase.(ABSTRACT TRUNCATED AT 250 WORDS)