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Journal of Lipid Research, Vol. 45, 1528-1537, August 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Evidence that hepatic lipase deficiency in humans is not associated with proatherogenic changes in HDL composition and metabolism

Isabelle L. Ruel^*,, Patrick Couture, Jeffrey S. Cohn, Andre Bensadoun^**, Michel Marcil and Benoit Lamarche^1,*,

^* Institute on Nutraceuticals and Functional Foods, Laval University, Québec City, Québec, Canada
Lipid Research Center, Laval University Hospital Center Research Center, Québec City, Québec, Canada
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal, Montréal, Québec, Canada
^** Division of Nutritional Sciences, Cornell University, Ithaca, NY
Cardiovascular Genetics Laboratory, Royal Victoria Hospital, McGill University Health Center, Montréal, Québec, Canada

¹ To whom correspondence should be addressed. e-mail: benoit.lamarche{at}inaf.ulaval.ca

The aim of the present study was to characterize the composition and metabolism of HDL in subjects with complete hepatic lipase (HL) deficiency. Analyses were carried out in three complete and three partial HL-deficient subjects as well as in eight normotriglyceridemic (NTG) and two hypertriglyceridemic controls. Complete HL deficiency was associated with hypertriglyceridemia and with a 3.5-fold increase in HDL-triglyceride (TG) levels. The in vivo kinetics of apolipoprotein A-I (apoA-I) and apoA-II (d < 1.25 g/l) were studied in the fasted state using a primed-constant infusion of L-(5,5,5-D₃)leucine for 12 h. Complete HL deficiency was associated with a reduced fractional catabolic rate of apoA-I in the HL-deficient female proband (–47%) and in her two brothers (–21%) compared with gender- and TG-matched controls. Total plasma and HDL from complete HL-deficient patients were able to mediate normal cholesterol efflux from human skin fibroblasts labeled with [³H]cholesterol. Complete HL deficiency was also associated with normal levels of preß-migrating apoA-I-containing HDL separated by two-dimensional gel electrophoresis and with an accumulation of large HDL particles compared with NTG controls.

These results suggest that HL activity is important for adequate HDL metabolism, although its presence may not be necessary for normal HDL-mediated reverse cholesterol transport.

Abbreviations: apoA-I, apolipoprotein A-I; CAD, coronary artery disease; CETP, cholesteryl ester transfer protein; EL, endothelial lipase; FCR, fractional catabolic rate; HL, hepatic lipase; HTG, hypertriglyceridemic; NTG, normotriglyceridemic; 1D-PAGGE, one-dimensional polyacrylamide gradient gel electrophoresis; QHLD, Québec-based hepatic lipase deficiency; RCT, reverse cholesterol transport; TG, triglyceride

Supplementary key words kinetics • high density lipoprotein • cholesterol efflux

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