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Presented in part at the 65th Scientific Sessions of the American Heart Association, New Orleans, La, and published in abstract form (Circulation. 1992;86[suppl I]:I-71.)
From the Laboratoire de Biochimie des Lipoprotéines, INSERM CJF 93-10, Faculté de Médecine, Dijon, France.
Correspondence to Laurent Lagrost, Laboratoire de Biochimie Médicale, Hôpital du Bocage, 21034 Dijon, France.
Abstract The relations between the level of plasma
nonesterified fatty acid (NEFA) and both the mass concentration and
activity of the cholesteryl ester transfer protein (CETP) were studied
in fasted normolipidemic subjects. Plasma NEFA correlated positively
with both CETP mass concentration (r=.50; P<.01)
and the transfer of cholesteryl ester from HDL toward plasma VLDL+LDL
(CETHDL
VLDL+LDL activity) (r=.46;
P<.05) but not with the transfer of cholesteryl ester from
LDL toward plasma HDL (CETLDL
HDL activity)
(r=-.05; NS). The high binding capacity of
albumin for NEFA was used to investigate whether
lipoprotein-bound NEFAs were implicated in the modulation of the
cholesteryl ester transfer reaction. As compared with nonsupplemented
controls, the addition of an excess of fatty acidfree
albumin (8 g/L) to total normolipidemic plasmas reduced
CETHDL
VLDL+LDL activity (18.3±5.5% versus 9.8±3.1%;
P<.0001) but not CETLDL
HDL activity
(22.3±4.5% versus 23.3±5.1%; NS). Moreover,
CETHDL
VLDL+LDL and CETLDL
HDL activities
correlated negatively when measured in native plasma
(r=-.45; P<.05) but positively when measured in
albumin-supplemented plasma (r=.40;
P<.05). In long-term incubation experiments,
lipoprotein-bound NEFA increased the net mass transfer of
cholesteryl esters from HDL toward VLDL+LDL but reduced the net mass
transfer of triglycerides in the opposite direction, from
VLDL+LDL toward HDL. Taken together, data of the present study
brought strong and concordant arguments in favor of a dual effect of
plasma NEFA in modulating both the mass and the activity of CETP in
vivo.
Key Words: plasma lipoprotein cholesteryl ester triglyceride cholesteryl ester transfer protein
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