Recycling of apolipoprotein E and lipoprotein lipase through endosomal compartments in vivo

We have recently described a novel recycling pathway of triglyceride-rich l ipoprotein (TRL)-associated apolipoprotein (apo) E in human hepatoma cells. We now demonstrate that not only TRL-derived apoE but also lipoprotein lip ase (LPL) is efficiently recycled in vitro and in vivo. Similar recycling k inetics of apoE and LPL in normal and low density lipoprotein receptor-nega tive human fibroblasts also indicate that the low density lipoprotein recep tor-related protein seems to be involved. Intracellular sorting mechanisms are responsible for reduced lysosomal degradation of both ligands after rec eptor-mediated internalization. Immediately after internalization in rat li ver, TRLs are disintegrated, and apoE and LPL are found in endosomal compar tments, whereas TRL-derived phospholipids accumulate in the perinuclear reg ion of hepatocytes. Subsequently, substantial amounts of both proteins can be found in purified recycling endosomes, indicating a potential resecretio n of these TRL components. Pulse-chase experiments of perfused rat livers w ith radiolabeled TRLs demonstrated a serum-induced release of internalized apoE and LPL into the perfusate. Analysis of the secreted proteins identifi ed similar to 80% of the recycled TRL-derived proteins in the high density lipoprotein fractions. These results provide the first evidence that recycl ing of TRL-derived apoE and LPL could play an important role in the modulat ion of lipoproteins in vivo.