ROLE OF FATTY-ACID-BINDING PROTEIN ON HEPATIC PALMITATE UPTAKE

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.