Secretion of nascent lipoproteins and apolipoproteins by perfused livers of normal and cholesterol-fed guinea pigs.

Abstract

Triglyceride-rich very low density lipoproteins (VLDL) are the major lipoprotein in perfusates of normal guinea pig livers. Their component apoprotein B is mainly B-100 together with some B-95. This apoprotein is actively synthesized, as are C apoproteins and small amounts of apoprotein E. Only trace amounts of intermediate density lipoproteins (IDL, 1.015 < d < 1.05 g/ml) are found in perfusates, but appreciable amounts of low density lipoproteins (LDL, 1.05 < d < 1.10 g/ml) accumulate. These LDL are not newly synthesized, but rather appear to be gradually washed out of the liver. High density lipoproteins (HDL, 1.10 < d < 1.21 g/ml) both discoidal and spheroidal, also accumulate, which contain newly synthesized apoproteins A-I, E and C. Fatty livers of guinea pigs fed cholesterol secrete less VLDL and more IDL than normals, but the combined amount of protein is unchanged. These lipoproteins contain newly synthesized apoprotein B, are enriched in cholesteryl esters and newly synthesized apoprotein E, and have reduced electrophoretic mobilities, making them resemble remnants. Large amounts of LDL also accumulate in perfusates of livers from cholesterol-fed animals, much of which does not appear to be newly synthesized, as judged from single pass perfusions. However, the LDL fraction is complex and includes particles that contain newly synthesized apoprotein B. Thus, these livers appear to secrete a spectrum of cholesteryl ester-rich particles, containing newly synthesized apoproteins B and E that span the density range of VLDL, IDL, and LDL. Livers of cholesterol-fed guinea pigs secrete large amounts of discoidal HDL with a free cholesterol-phospholipid molar ratio of 2:1. Accumulation of protein (almost entirely newly synthesized apoprotein E) in HDL is increased 25-fold over that in perfusates from normal guinea pig livers.-Guo, L.S.S., R.L. Hamilton, R. Ostwald, and R. J. Havel. Secretion of nascent lipoproteins and apolipoproteins by perfused livers of normal and cholesterol-fed guinea pigs.