Inhibition of binding to fatty acid binding protein (fabp) reduces
the intracellular transport of fatty acids.
Luxon, Bruce A.
Division of Gastroenterology and Hepatology, P. O. Box 15250, St.
Louis University Health Sciences Center, St. Louis, MO 63110-0250
APStracts 3:0026G, 1996.
Male livers, containing lesser amounts of fatty acid binding protein
(FABP) utilize fatty acids more slowly than female livers.
Conventional wisdom dictates that FABP stimulates fatty acid use by
increasing cytoplasmic transport rates. Previously we showed that the
cytoplasmic diffusion of a fatty acid analog (NBD-stearate) is faster
in female hepatocytes, paralleling the larger amounts of FABP. Sex
differences in other cytoplasmic factors could also lead to faster
diffusion, independent of FABP levels. The aim of this study was to
determine the effect of inhibition of fatty acid binding to FABP on
the directly measured intracellular transport rate of NBD-stearate.
The binding of NBD-stearate to FABP was reduced by incubating
hepatocytes isolated from male and female rats with a-bromo-palmitate
(0-1500 M), a modified long chain fatty acid that binds to FABP. The
inhibition by a-bromo-palmitate on NBD-stearate binding to FABP was
measured using centrifugation to separate cytosol from cytoplasmic
membranes. Laser photobleaching (FRAP) was used to measure the
cytoplasmic diffusion of NBD-stearate in hepatocytes. a-bromo
-palmitate incubation reduced NBD-stearate binding to FABP in a dose
-dependent manner. The measured diffusion rate was also reduced in
proportion to the degree of binding inhibition. We conclude that
cytoplasmic transport of NBD-stearate is modulated by binding to
soluble proteins like FABP. FABP enhances diffusive transport by
reducing binding to immobile cytosolic membranes.
Received 18 July 1995; accepted in final form 9 January 1996.
APS Manuscript Number G298-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96