Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol.
OBJECTIVE
We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol.


METHODS
In 76 subjects with and 94 subjects without MetS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined plasma (apo)lipoproteins, pre-beta-HDL formation, phospholipid transfer protein (PLTP) activity, cholesterol esterification (EST), cholesteryl ester transfer (CET), adiponectin, and the ability of plasma from each subject to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single donor.


RESULTS
Apo E, PLTP activity, EST, and CET were higher (P=0.04 to <0.001), whereas adiponectin was lower in MetS subjects (P<0.01). Pre-beta-HDL and pre-beta-HDL formation were not different between subjects with and without MetS. Cellular cholesterol efflux to plasma from MetS subjects was slightly higher versus plasma from subjects without MetS (8.8+/-1.0 vs 8.5+/-0.9%, P=0.05), but the difference was not significant after age, sex, and diabetes adjustment. Cellular cholesterol efflux was positively related to pre-beta-HDL formation, EST, PLTP activity, and apo E (P<0.05 for all by multiple linear regression analysis), without an independent association with MetS and diabetes status.


CONCLUSIONS
The ability of plasma from MetS subjects to promote fibroblast cholesterol efflux is not defective, although HDL cholesterol is decreased. Higher cholesterol esterification, PLTP activity, and apo E levels may contribute to the maintenance of cholesterol efflux in MetS.
Dullaart
Robin P F
RP
Department of Endocrinology, University of Groningen and University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. r.p.f.dullaart@int.umcg.nl
Groen
Albert K
AK
Dallinga-Thie
Geesje M
GM
de Vries
Rindert
R
Sluiter
Wim J
WJ
van Tol
Arie
A
D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins / Q000097:blood; D010949:Plasma / Q000378:metabolism*
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D049294:Phospholipid Transfer Proteins; D002784:Cholesterol