Role of fatty acid binding protein on hepatic palmitate uptake.
Expression of hepatic fatty acid binding protein (FABP) mRNA is regulated by growth hormone. In the absence of growth hormone, there is a 60% reduction in FABP mRNA levels (S.A. Berry, J.-B Yoon, U. List, and S. Seelig. J. Am. Coll. Nutr. 12:638-642. 1995). Previous work in our laboratory focused on the role of extracellular binding proteins in the hepatic uptake of long chain fatty acids. In the present study we were 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 [3H]palmitate in the presence and absence of albumin. In the absence of albumin, total hepatocyte [3H]palmitate clearance rates from control (17.2 +/- 1.5 microL.mg-1 protein.s-1; mean +/- SEM; n = 9) and hypophysectomized (15.5 +/- 2.1 microL.mg-1 protein.s-1; n = 6) animals were similar (p > 0.05). In the presence of 2 microM albumin the total [3H]palmitate clearance rate from control hepatocytes (1.63 +/- 0.11 microL.mg-1 protein.s-1; n = 9) was significantly larger (40%) than from hepatocytes obtained from hypophysectomized (0.97 +/- 0.15 microL.mg-1 protein.s-1; n = 6; p < 0.01) animals. SDS-PAGE electrophoresis revealed that plasma membrane FABP levels from control and hypophysectomized animals were similar. However, there was a 49% decrease in the cytosolic FABP levels of hepatocytes isolated from hypophysectomized as compared with control animals. The decreased cytosolic FABB levels 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 long chain fatty acids is diffusion to the cell surface. However, in the presence of albumin, the rate of palmitate uptake is determined primarily by cytosolic FABP levels.
Burczynski
F J
FJ
Division of Pharmaceutical Sciences, Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada. burczyn@cc.umanitoba.ca
Zhang
M N
MN
Pavletic
P
P
Wang
G Q
GQ
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002463:Cell Membrane Permeability; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D018996:Myelin P2 Protein / Q000502:physiology*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010168:Palmitates / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology
D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010168:Palmitates; D012333:RNA, Messenger; D012709:Serum Albumin