Lipoprotein lipase degradation by adipocytes: receptor-associated protein (RAP)-sensitive and proteoglycan-mediated pathways.

Lipoprotein lipase (LPL), the major enzyme re- sponsible for the hydrolysis of triglycerides, is primarily syn- thesized by adipocytes and myocytes. In addition to synthesis, degradation of cell surface-associated LPL is thought to be important in regulating production of the enzyme. We stud- ied LPL metabolism in the LPL synthesizing adipocyte cell line BFGlP and assessed the contributions of cell surface he- paran sulfate proteoglycans (HSPG), low density lipoprotein receptor related protein (LRP) , and glycosylphosphatidylinos- itol (GP1)-linked proteins to LPL uptake and degradation by these cells. Adipocytes degraded IO-12% of total cell surface '251-labeled LPL in 2 h and 23-28% in 4 h. In 1 h, 30-54% of the degradation was inhibited by the 39 kDa receptor assc- ciated protein (RAP), an inhibitor of ligand binding to LRP. At 4 h, only 19-23% of the LPL degradation was RAP inhibit- able. This suggested that two pathways with different kinetics were important for LPL degradation. Heparinase/ hepariti- nase treatment of cells showed that most LPL degradation required the presence of HSPG. Treatment with phospha- tidylinositol-specific phospholipase C (PIPLC) inhibited labeled LPL degradation by 13%. However, neither RAP nor PIPLC treatment of adipocytes significantly increased the amount of endogenously produced LPL activity in the media. To determine whether direct uptake of LPL bound to HSPG could account for the non-RAP sensitive LPL uptake and deg- radation, proteoglycan metabolism was assessed by labeling cells with %04. Of the total pericellular proteoglycans, 14% were PIPLC releasable; surprisingly, 30% were dissociated from the cells with heparin. The amount of labeled pericellu- lar proteoglycans decreased 26% in 2 h and 50% in 8 h, rapid enough to account for at least half of the degradation of cell surface LPL.W We conclude that adipocytes degrade a frac- tion of the cell surface LPL, and that this process is mediated by both proteoglycans and RAP-sensitive receptors.-Obun- &e, J. C., P. Sivaram, L. Paka, M. G. Low, and I. J. Goldberg. Lipoprotein lipase degradation by adipocytes: receptor-associ- ated protein (RAP)-sensitive and proteoglycan-mediated path- ways. J. Lipid Res. 1996. 37: 2439-2449.