Transfer of newly made triglyceride from hepatocytes to preexisting extracellular very low density lipoproteins

Previous in vivo studies suggested a new model to describe the metabolism of very low density lipoproteins (VLDL). It was hypothesized that some of the lipoprotein triglyceride was transferred directly from hepatocytes and intestinal mucosal cells into preexisting extracellular VLDL particles. These studies employ an in vitro system to test this hypothesis. Isolated rat liver cells containing newly made radioactive triglyceride were prepared. These cells were incubated in medium to which exogenous VLDL had or had not been added. The presence of extracellular VLDL (rat or human) stimulated the transfer of labeled triglyceride out of the liver cells. This triglyceride was recovered in the medium's VLDL (as determined by its density and its precipitability by MnCl2–heparin or by anti-apoprotein B). Although these studies focussed on VLDL, preliminary data showed that similar triglyceride transfer occurred in the presence of the other apoprotein B containing lipoprotein, low density lipoprotein (LDL). However, in the presence of equivalent amounts of LDL, this triglyceride transfer was less than that seen in the presence of exogenous VLDL. Furthermore, the increased triglyceride released in the presence of LDL occurred entirely in the d < 1.006 fraction of the medium. That released in the presence of VLDL was recovered in the d > 1.006 fraction. Hence, we conclude that the transfer of the newly made triglyceride was from the cell to the extracellular lipoprotein that had been added to the medium. The transfer of triglyceride to VLDL did not depend on the synthesis and release of new VLDL particles because it was not accompanied by a change in the production of [14C]leucine VLDL protein, it was not blocked by chloroquine, and the LDL induced triglyceride release occurred into the d > 1.006 fraction. This transfer did not depend on the previously described triglyceride-transfer factor. The present in vitro studies support the model suggested by our earlier in vivo studies. The VLDL particle does not appear to be metabolized as a complete intact unit. Rather, some of its major lipid component, triglyceride, can move directly into and out of already existing extracellular lipoproteins.