Effect of desialylation of very low-density lipoproteins on their catabolism by lipoprotein lipase.
Very low-density lipoproteins (VLDL) contain sialylated apolipoproteins (apo) (eg, apo CIII1-3) that inhibit apo CII activation of lipoprotein lipase (LPL) and also uptake of triglyceride (TG)-rich lipoproteins by the liver. Hypertriglyceridemic patients can have an excess of sialylated apo CIII (apo CIII1 or apo CIII2) in VLDL. These observations have prompted the notion that sialic acid in VLDL may impede LPL or receptor-mediated clearance of VLDL and thus result in hypertriglyceridemia. The aim of this study was to determine whether desialylation of VLDL altered their property as a substrate for LPL. VLDL isolated from five hypertriglyceridemic patients was desialylated with neuraminidase, labeled with a fluorescent probe, dansyl phosphatidylethanolamine and 600 micrograms of labeled VLDL TG were incubated with a constant amount of purified bovine LPL. The change in fluorescence against time was monitored on a recorder to yield curves representing continuous lipolysis of VLDL by LPL. Mean initial velocity of reaction (Vi) and extent of lipolysis measured as total increase in fluorescence over baseline at 30 minutes (F30/FO) were similar (Vi = 10.2 +/- 0.37 control v 10.2 +/- 0.42 u/min desialylated VLDL; F30/FO = 4.1 +/- 0.15, control v 4.1 +/- 0.07 desialylated VLDL; n = 5). Thus, sialic acid does not influence VLDL catabolism by LPL. Our study does not exclude a possible role of the sialic acid in receptor mediated uptake of remnants produced by initial catabolism of VLDL by LPL.
D000328:Adult; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007525:Isoelectric Focusing; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D008079:Lipoproteins, VLDL; D012794:Sialic Acids; D008071:Lipoprotein Lipase; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid