The effect of human C apolipoproteins on the in vitro hepatic metabolism of triglyceride emulsions in the rat.

The effect of human C-I, C-11, and C-111-2 apolipoproteins on the metabolism of triglyceride in triglyceride emulsions was studied in the in vitro perfused rat liver and the nonreplicating hepatocyte monolayer culture. All three human apolipoproteins delayed hepatic uptake of the triglyceride emulsion, both when the emulsion was supplemented with human apolipoprotein E and without this apolipoprotein. The inhibition produced by the C-111-2 protein was reproducible from study to study and was greater than that produced by the other two apoproteins. Inhibition of hepatic triglyceride uptake by both the C-I and C-I1 protein was variable from study to study. However, the mean uptake was significantly less than control for both of these apoproteins. The hepatic uptake of the ‘251-apolipoprotein E associated with the emulsion was somewhat similar to that of the triglyceride in those perfusions without C apolipoproteins. Perfusions with added C apoproteins demonstrated a significant inhibition of hepatic triglyceride uptake but little change in the uptake of the associated lZ5I-E apoprotein when compared to perfusions without these apoproteins. When the triglyceride was introduced into the liver at the start of an isolated hepatic perfusion, little radioactive triglyceride appeared in the perfusates of the control animals. The presence of the apolipoprotein C proteins, particularly C-111-2, in the perfusate produced a significant increment in the total recovery of radiolabeled lipid and enhanced the partition of triglyceride into the perfusate. The fractional conversion of albumin-bound free fatty acid to media triglyceride was appreciably greater in nonreplicating rat hepatocyte monolayer cultures to which C apoproteins had been added. Studies of nonreplicating rat hepatocyte monolayer cultures revealed influences of the C proteins on the uptake of triglyceride emulsions similar to those seen i the liverperfusion studies. The C-111-2 protein had the most pronounced inhibitory effect on uptake with less but still significant inhibition observed for the C-I1 and CI proteins. Similar effects were observed for the C proteins in incubations of human erythrocytes with triglyceride emulsions. The C-111-2 protein significantly reduced the association of emulsion triglyceride with these cells both in the presence and absence of the E protein. In liver perfusions and hepatocyte cultures, egg phosphatidylcholine decreased the uptake of triglyceride emulsions and partially reversed the inhibition produced by the C-111-2 protein.