DIFFERENTIAL BINDING OF TRIGLYCERIDE-RICH LIPOPROTEINS TO LIPOPROTEIN LIPASE

In comparison to very low density lipoprotein (VLDL), chylomicrons are cleared quickly from plasma. However, small changes in fasting plasma VLDL concentra- tion substantially delay postprandial chylomicron triglycer- ide clearance. We hypothesized that differential binding to lipoprotein lipase (LPL), the first step in the lipolytic path- way, might explain these otherwise paradoxical relation- ships. Competition binding assays of different lipoproteins were performed in a solid phase assay with purified bovine LPL at 4 8 C. The results showed that chylomicrons, VLDL, and low density lipoprotein (LDL) were able to inhibit spe- cific binding of 125 I-labeled VLDL to the same extent (85.1% 6 13.1, 100% 6 6.8, 90.7% 6 23.2% inhibition, P 5 NS), but with markedly different efficiencies. The rank or- der of inhibition ( K i ) was chylomicrons (0.27 6 0.02 n M apoB) . VLDL (12.6 6 3.11 n M apoB) . LDL (34.8 6 11.1 n M apoB). By contrast, neither triglyceride (TG) liposomes, high density lipoprotein (HDL), nor LDL from patients with familial hypercholesterolemia were efficient at displacing the specific binding of 125 I-labeled VLDL to LPL (30%, 39%, and no displacement, respectively). Importantly, smaller hydrolyzed chylomicrons had less affinity than the larger chylomicrons ( K i 5 2.34 6 0.85 n M vs. 0.27 6 0.02 n M apoB respectively, P , 0.01). This was also true for hydro- lyzed VLDL, although to a lesser extent. Chylomicrons from patients with LPL deficiency and VLDL from hypertriglyc- eridemic subjects were also studied. Taken together, our results indicate an inverse linear relationship between chylo- micron size and K i whereas none was present for VLDL. We hypothesize that the differences in binding affinity demon- strated in vitro when considered with the differences in par- ticle number observed in vivo may largely explain the para- doxes we set out to study. —Xiang, S-Q., K. Cianflone, D. Kalant, and A. D. Sniderman. Differential binding of triglyc- eride-rich lipoproteins to lipoprotein lipase. J. Lipid Res. 1999. 40: 1655-1662.