Journal of Lipid Research, Vol 19, 1025-1031, Copyright © 1978 by Lipid Research, Inc.
Antilipolytic effects of chlorophenoxyisobutyrate and warfarin in adipocytes
H Meisner and S Taylor
This study was designed to examine whether displacement of free fatty acids
(FFA) from albumin (BSA) can explain the antilipolytic effect of
chlorophenoxyisobutyrate (CPIB). Warfarin, which binds to albumin with
equal affinity, was used to test the generality of this mechanism. The
procedure was to measure the concentration of free drug needed to inhibit
hormone-stimulated lipolysis in isolated rat epididymal fat cells, and the
effect on this process of albumin, which binds both FFA ligand and drug.
The free drug concentration was initially obtained by ultrafiltration
studies with albumin and 14C-labeled CPIB or 14C- labeled warfarin in the
absence of cells. When epinephrine-activated lipolysis was measured,
inclusion of 0.3 mM albumin decreased the free CPIB concentration required
for 50% inhibition from 1.8 mM (-BSA) to 0.08 mM. Warfarin also inhibited
lipolysis more effectively in the presence of albumin, with 50% inhibition
at 0.06 mM (+BSA) vs. 0.7 mM (- BSA). Both drugs showed a similar
high-affinity binding constant to albumin of n = 1, k = 2--4 X 10(5) M-1,
and both competitively displaced [14C]stearate, provided that a hydrophobic
trap was present. The results are consistent with the possibility that the
antilipolytic effect of CPIB and warfarin is mediated by way of a
competitive displacement of FFA from albumin, or an analogous cellular
binding site, with subsequent feedback inhibition of lipolysis.
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