Post-secretory acquisition of apolipoprotein E by nascent rat hepatic very-low-density lipoproteins in the absence of cholesteryl ester transfer

Previous work has shown that nascent hepatic very-low-density lipoproteins (VLDL) in the rat are biosynthesized without the obligatory co-factor (apolipoprotein C-II) for lipoprotein lipase-mediated hydrolysis of their core triacylglycerols. Upon secretion, apolipoproteins C-II and C-III are rapidly transferred to the particles from high-density lipoprotein (HDL) within the space of Disse and upon the entry into the plasma. Here we extend those studies to include observations on the apolipoprotein E content and lipid composition of nascent hepatic VLDL before and after exposure to plasma components. We have elected to use hepatic secretory vesicle VLDL rather than liver perfusate VLDL as truly representative of the nascent lipoproteins. Nascent VLDL from fed rats has an apolipoprotein B/E ratio of 6.6 ± 0.5, whereas that from fasted animals is 13.9 ± 2.3. Incubation of nascent VLDL from fed and fasted rats with d > 1.063 g/ml rat serum, HDL or the d > 1.21 g/ml fraction resulted in a mass transfer of apoliproprotein E to the VLDL such that the apolipoprotein B/E ratio decreased to at least that of serum VLDL (3.4 ± 0.3). The d > 1.21 g/ml fraction appeared to contain a species of apolipoprotein E which most actively transferred to VLDL. The acquisition of apolipoprotein E by nascent secretory vesicle VLDL was attended by a loss of phospholipids, particularly the C₄₀ (stearoylarachidonyl) molecular species, and an increase in the cholesterol-to-phospholipid ratio from 0.11 ± 0.01 to 0.18 ± 0.03. No evidence was obtained to suggest a simultaneous acquisition of cholesteryl esters upon incubation of nascent VLDL with VLDL-free serum. We conclude that nascent hepatic VLDL is modified after secretion by acquisition of apolipoproteins C-II, C-III and E with a concomitant loss of phospholipids.