VLDL-bound lipoprotein lipase facilitates the cholesteryl ester transfer protein-mediated transfer of cholesteryl esters from HDL to VLDL.
In recent years, it has been established that lipoprotein lipase (LPL) is partly associated with circulating lipoproteins. This report describes the effects of physiological amounts of very low density lipoprotein (VLDL)-bound LPL on the cholesteryl ester transfer protein (CETP)-mediated cholesteryl ester transfer (CET) from high density lipoprotein (HDL) to VLDL. Three patients with severe LPL deficiency exhibited a strong decrease in net mass CET that was more than 80% lower than that of common hypertriglyceridemic subjects. Recombination experiments showed that this was due to an abnormal behavior of the VLDL fraction. Replacement of the latter by normal VLDL totally normalized net mass CET. We therefore prepared VLDL containing controlled amounts of bound LPL that we used as CE acceptors in experiments involving unidirectional radioisotopic CET measurements. These were carried out either in the absence or in the presence of inhibitors of LPL lipolytic activity. When LPL-induced lipolysis was totally blocked, the stimulating effect of the enzyme on the CETP-dependent CET was only reduced by about 50%, showing that it did not entirely result from its lipolytic action. These data were dependent upon neither the type of LPL inhibitor (E600 or THL) nor the source of CETP (delipidated plasma or partially purified CETP). Thus, in addition to the well-known stimulating effect of LPL-dependent lipolysis on CET, our work demonstrates that physiological amounts of VLDL-bound LPL may facilitate CET through a mechanism partially independent of its lipolytic activity.
Pruneta
V
V
Laboratoire de Métabolisme des Lipides, Centre Hospitalier Lyon-Sud, Lyon, France.
Pulcini
T
T
Lalanne
F
F
Marçais
C
C
Berthezène
F
F
Ponsin
G
G
Moulin
P
P
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D006023:Glycoproteins; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000187:drug effects / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D008071:Lipoprotein Lipase; D019791:Guanidine