European Journal zyxwvutsrqp of Clinical Investigation zyxwvuts (1 zyxwvutsr 990) 20,422-43 1 zyxwvu ln vitro zyxwv remodelling of plasma lipoproteins in whole plasma by lipoprotein lipase in primary and secondary hypertriglyceridaemia E. LEVY, R. J. DECKELBAUM*, R. L. THIBAULT, E. SEIDMAN, T. OLIVECRONAt & C. C. ROY, Departments of Gastroenterology and Nutrition, University of Montreal and Research Center, Sainte-Justine Hospital, Montreal, Quebec, Canada, *Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, USA, and ?Department of Physiological Chemistry, University of Umea, Umea, Sweden Received 1 August 1989 and in revised form 9 January 1990 zyxwv Abstract. In patients with familial lipoprotein lipase deficiency (FLPL-d) and glycogen storage disease type I (GSD-I), hypertriglyceridaemia (1445 zyxwvu f 247 and 1082 3 12 mg dl- ‘, n = 5 per group) was associated primarily with reduced extrahepatic lipoprotein lipase (LPL) activity (0.33 f0.33 and 1.69kO.38 pmol FFA ml-’ h-I) when compared with controls (4.83f0.90). Hypercholesterolaemia was characterized by elevated LDL cholesterol (I91 f 30 and 344 f 34 vs. 1 15 5 mg dl-’ in controls P<O.OI) and low HDL cholesterol (12+2and22&2vs. 56f3incontrols, P<O.OOI). In order to ascertain the role of LPL in the interconver- sion and remodelling of lipoproteins in these disorders, we analysed lipid and lipoprotein profiles before and following in uitro incubation of patient plasma with purified milk LPL (EC 3. I. 1.34) for 6 h at 37°C. The efficiency of exogenous LPL in uitro was demonstrated by the extent of hydrolysis of chylomicrons and of VLDL-TG in both groups. Concomitant with the disappearance of TG-rich lipoprotein particles, a consistent per cent increment of IDL (99.2 f 30.8 and 43.9 k 70.5), LDL (152.8 f 36.2 and 137.0 f 36- 1) and of HDLz(144.8 f 29.4 and 99.8 & 18.7) was observed in both groups of patients. The enhancement of the latter fractions contrasted with the decline of HDL3 mass concentration (25.4 f 7.7 and 5 1.4f 5.8%), suggesting that a major shift of HDL3+HDL2 occurs following in uitro lipolysis by LDL. Simultaneous compositional and morphological changes of individual lipoprotein particles were noted, confirming the dynamic move- ment and exchange of neutral lipids and proteins. Specificity of LPL results was demonstrated by experi- ments in which incubation of the whole plasma at 37°C without exogenous lipolytic enzyme did not cause any substantial changes. The present study, therefore, demonstrates a correction of the major lipoprotein abnormalities associated with FLPL-d and GSD-I by exogenous LPL. No substantial difference was noted Correspondence: E. Levy, Gastroenterology and Nutrition Unit, Hhpital Sainte-Justine, 3175 Sainte-Catherine Road, Montreal, Quebec, H3T 1C5, Canada. between primary (FLPL-d) and secondary (GSD-I) hyperlipidaemias. These studies allow us to conclude that a simple in uitro system, utilizing an exogenous source of LPL and plasma from patients, may serve as a suitable model for the study of the metabolic relationships of lipoproteins. However, in view of the fact that the extent of lipolysis achieved in uitro did not differ between FLPL-d and GSD-I, it may not be able to separate primary from secondary hyperlipaemias. Keywords. Glycogen storage disease type I; familiar lipoprotein lipase deficiency; chylomicron; VLDL; IDL; LDL; HDL,; apoprotein. Introduction Lipoprotein lipases have an important role in the regulation of serum lipoprotein metabolism, composi- tion and structure [I-31. Chylomicrons (CM) and very- low-density lipoproteins (VLDL) are hydrolysed by LPL bound to the capillary endothelium of adipose tissue, heart, skeletal muscle, lung and milk [ 1,4]. In the catabolic process, CMs are rapidly degraded to form remnants and VLDLs that are sequentially lipolysed to produce IDL and LDL [5]. The constituents originat- ing from the surface coat (phospholipids, free choles- terol and apoproteins) of hydrolysed TG-rich lipopro- teins are thought to undergo transfer to HDL3, thereby promoting its conversion to HDL2 [5-81. LPL activity is, therefore, related to the levels of plasma HDL, particularly the HDL2 subfraction [7,8]. Based on these observations, it would appear that plasma lipolysis constitutes not only a delivery source of fatty acids to peripheral tissues, but also an important route for the modulation of the structure and concentration of lipoproteins. Prior reports suggesting a regulatory role for LPL in the concentration and spectrum of HDL are primarily based on population studies and on the results of various treatment regimens [9- 121. However, few 422