Lipoprotein secretion by isolated rat hepatocytes: characterization of the lipid-carrying particles and modulation of their release.

Lipoprotein production by freshly isolated rat hepatocytes in suspension was studied during short (1--3 hr) incubation periods. The hepatocytes release very low density (d < 1.01 g/ml) lipoprotein (VLDL) particles, which as a group a) contain triaclyglycerols, phospholipids, free cholesterol, and cholesteryl esters in molar proportions of 100:21:8:4; b) have a mean diameter 1.5-fold larger than those of plasma VLDL; c) have a similar electrophoretic mobility as plasma VLDL; and d) carry apoproteins B and E as major, and apoproteins AI and C as minor, protein components. These apoproteins in the secreted VLDL can be newly synthesized during the incubation, as indicated by the incorporation of [14C]leucine. The secretion of VLDL by the hepatocytes is inhibited by addition of glucagon or dibutyryl cyclic AMP, and stimulated by added palmitate; thus, as in the whole liver, the secretory process is under hormonal or substrate control also in the isolated cells condition. Phospholipids and free cholesterol are also released as components of particles with higher densities, ranging from 1.03--1.08 g/ml, and from 1.10 to 1.24 g/ml. Colchicine and cycloheximide, while strongly suppressing VLDL secretion, inhibit the release of these other particles to a lesser extent (d 1.03--1.08 g/ml) or not at all (d > 1.10 g/ml). These particles with higher densities have not been positively identified; the latter group is dissimilar to the high density lipoprotein, which occurs in rat liver perfusates, or to rat bile micelles.