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Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1388-1396

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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1388-1396.)
© 1995 American Heart Association, Inc.


Articles

Evidence for Nonesterified Fatty Acids as Modulators of Neutral Lipid Transfers in Normolipidemic Human Plasma

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.)

Laurent Lagrost; Emmanuel Florentin; Valérie Guyard-Dangremont; Anne Athias; Hassan Gandjini; Christian Lallemant; Philippe Gambert

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 acid–free 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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