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Papers In Press, published online ahead of print June 1, 2004
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Institute on Nutraceuticals and Functional Foods, Laval University, Quebec, Qc G1K 7P4
Corresponding Author: 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 3 complete and 3 partial HL-deficient subjects as well as in 8 normotriglyceridemic (NTG) and 2 hypertriglyceridemic (HTG) controls. Complete HL deficiency was associated with hypertriclyceridemia and with a 3.5-fold increase in HDL-TG levels. The in vivo kinetics of 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 reduced fractional catabolic rate (FCR) 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 pre-beta-migrating apoA-I-containing HDL separated by two-dimensional gel electrophoresis, and with an accumulation of large HDL particles compared to NTG controls. These results suggest that HL activity is important for adequate HDL metabolism though its presence may not be necessary for normal HDL-mediated reverse cholesterol transport.
Revised on May 12, 2004
Accepted on May 18, 2004
Evidence that hepatic lipase deficiency in humans is not associated with proatherogenic changes in HDL composition and metabolism
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