Cytosolic fatty acid binding protein enhances rat hepatocyte [3H]palmitate uptake.
Liver cytosolic fatty acid binding protein (FABP) represents the intracellular equivalent to extracellular serum albumin, participating in the intracellular transport of long-chain fatty acids. In this study we observed the effect of increasing and decreasing FABP levels on hepatocyte [3H]palmitate uptake in male Sprague-Dawley rats. We also were interested to determine whether uptake, from either the unbound or unbound and protein-bound fractions, was fundamentally different at the different FABP levels. FABP levels were modified by hypophysectomy and clofibrate treatment (50 mg/100 g body weight for 10 days). Results showed that the [3H]palmitate clearance rates paralleled the 54% decrease and 73% increase in FABP levels in hypophysectomy and clofibrate-treated animals, respectively. In the presence of 2 and 20 microM albumin, hepatocyte clearance rates of unbound [3H]palmitate from hypophysectomized animals (0.16+/-0.01 and 0.64+/-0.01 mL x s(-1) x 10(-6) cells, respectively) were significantly lower (p<0.01) than those of the sham group (0.30+/-0.02 and 1.00+/-0.06 mL x s(-1) x 10(-6) cells, respectively). However, the unbound [3H]palmitate clearance rates from the clofibrate-treated group (0.39+/-0.04 and 1.18+/-0.12 mL x s(-1) x 10(-6) cells) were significantly higher (p<0.01) than the control group (0.29+/-0.02 and 0.81+/-0.05 mL x s(-1) x 10(-6) cells) for 2 and 20 microM albumin, respectively. To investigate whether uptake was fundamentally different between the hypophysectomized and clofibrate-treated groups, we expressed the clearance rates as enhancement factors, i.e., EF = CL20 microM/CL2microM. No statistical difference was observed between EF of the hypophsectomized (3.8+/-0.4) and EF of the clofibrate-treated (3.1+/-0.3) groups, suggesting that the extracted ligand originated from similar fractions.
Burczynski
F J
FJ
Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of Manitoba, Winnipeg, Canada. burczyn@cc.umanitoba.ca
Fandrey
S
S
Wang
G
G
Pavletic
P A
PA
Gong
Y
Y
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002994:Clofibrate / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D007016:Hypophysectomy; D008099:Liver / Q000378:metabolism*; D008297:Male; D018996:Myelin P2 Protein / Q000378:metabolism*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019308:Palmitic Acid / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012709:Serum Albumin; D019308:Palmitic Acid; D002994:Clofibrate