Studies on the synthesis and secretion of serum lipoproteins by rat liver slices.

There is at present a great deal of interest in factors determining the levels of serum lipids because of their possible relation to atherosclerosis. Since the serum lipids circulate only in the form of lipid-protein complexes, the mechanism of production of these complexes and their delivery into and removal from the serum must be understood before there is a sound basis for defining the homeostatic mechanisms controlling the levels of individual lipid components. While factors influe7ncing the metabolism of any one of the individual lipid moieties may influence the serum levels of that moiety, such an effect must ultimately be expressed indirectly through an alteration in the rate or pattern of metabolism of the lipid-protein complexes of which it is a part. The present experiments were undertaken in order to define an in vitro system in which lipoprotein biosynthesis could be studied without the many complicating variables encountered in whole-animal studies. It is generally accepted that the liver is the principal source of the serum lipids (1-3) and it has been assumed, but not proved, that the liver is also the source of the protein moiety of the serum lipoproteins. We have previously described the incorporation by perfused rat liver and by rat liver slices of labeled amino acids into proteins with densities similar to those of the serum lipoproteins (4, 5). The studies reported here provide evidence that the high density lipoproteins synthesized and secreted by rat liver slices are identical with the high density lipoproteins of normal rat serum. The time course of synthesis of both the protein and the lipid moieties in the total lipoprotein fraction, the rate of appearance of radioactive lipoprotein in the medium, and the net changes in protein and lipid in liver slice and medium are presented. The effects of cholesterol