Uptake of cholesterol from the very low density lipoprotein or its remnants by the perfused rat liver

Abstract

[3H]Cholesterol labeled very low density lipoproteins ([3H]chol-VLDL) were prepared to study the hepatic uptake of cholesterol associated with VLDL and its remnants in the perfused liver system. [3H]Chol-VLDL was incubated with rat postheparin plasma to produce labeled remnants in vitro. The degree of lipolysis of [3H]chol-VLDL depended on the ratio of triacylglycerols to lipase in the incubation medium. The produced remnant of d [density] < 1.019 g.cntdot.ml-1 had a variable lipid composition depending on the degree of lipolysis. [3H]Chol-VLDL or its remnants were added to liver perfusate and the radioactivity remaining in the perfusate was measured. The kinetic disappearance of [3H]chol-VLDL and its remnants in the perfused liver system indicated that remnant of d < 1.019 g.cntdot.ml-1 was taken up by the liver faster than the original VLDL preparation (t1/2 [half-time] of 8 min vs. 51 min). Appearance of the label in bile during the perfusion was significantly faster when livers were perfused with [3H]chol-VLDL remnants as opposed to uncatabolized [3H]chol-VLDL. VLDL remnants produced in vitro and reisolated at density < 1.019 g.cntdot.ml-1 do not have a fixed lipid composition but a rather variable one depending on the degree of lipolysis. The rat liver may preferentially recognize this VLDL remnant of d < 1.019 g.cntdot.ml-1 and take it up more readily than uncatabolized VLDL. When equimolar amount of cholesterol from VLDL or VLDL remnants are circulated in the liver perfusion, the VLDL remnants convey a significantly greater mass of cholesterol to the bile.