Fj. Burczynski et al., ROLE OF FATTY-ACID-BINDING PROTEIN ON HEPATIC PALMITATE UPTAKE, Canadian journal of physiology and pharmacology, 75(12), 1997, pp. 1350-1355
Expression of hepatic fatty acid binding protein (FABP) mRNA is regula
ted by growth hormone. In the absence of growth hormone, there is a 60
% reduction in FABP mRNA levels (S.A. Berry, J.-B. Yoon, J. List, and
S. Seelig. J. Am. Cell,. Nutr. 12: 638642. 1995). Previous work in our
laboratory focused on the role of extracellular binding proteins in t
he hepatic uptake of long chain fatty acids. In the present study we w
ere interested to determine the role of FABP in the transmembrane flux
of long chain fatty acids. Using hepatocyte monolayers from control (
n = 9) and hypophysectomized (n = 6) rats, we investigated the uptake
of [H-3]palmitate in the presence and absence of albumin. In the absen
ce of albumin, total hepatocyte [H-3]palmitate clearance rates from co
ntrol (17.2 +/- 1.5 mu L.mg(-1) protein.s(-1); mean +/- SEM; n = 9) an
d hypophysectomized (15.5 +/- 2.1 mu L.mg(-1) protein.s(-1); n = 6) an
imals were similar (p > 0.05). In the presence of 2 mu M albumin the t
otal [H-3]palmitate clearance rate from control hepatocytes (1.63 +/-
0.11 mu L.mg(-1) protein.s(-1); n = 9) was significantly larger (40%)
than from hepatocytes obtained from hypophysectomized (0.97 +/- 0.15 m
u L.mg(-1) protein.s(-1); n = 6; p < 0.01) animals. SDS-PAGE electroph
oresis revealed that plasma membrane FABP levels from control and hypo
physectomized animals were similar. However, there was a 49% decrease
in the cytosolic FABP levels of hepatocytes isolated from hypophysecto
mized as compared with control animals. The decreased cytosolic FABP l
evels paralleled the decrease in palmitate uptake. We conclude that in
the absence of extracellular binding proteins the rate-limiting step
in the overall uptake of Ion:: chain fatty acids is diffusion to the c
ell surface. However, in the presence of albumin, the rate of palmitat
e uptake is determined primarily by cytosolic FABP levels.