Cytosolic fatty acid binding protein enhances rat hepatocyte [3H]palmitate uptake

被引:16
作者
Burczynski, FJ
Fandrey, S
Wang, G
Pavletic, PA
Gong, Y
机构
[1] Univ Manitoba, Fac Pharm, Div Pharmaceut Sci, Winnipeg, MB R3T 2N2, Canada
[2] Univ Manitoba, Fac Med, Dept Pharmacol & Therapeut, Winnipeg, MB R3T 2N2, Canada
[3] Univ Manitoba, Fac Med, Dept Internal Med, Winnipeg, MB R3T 2N2, Canada
关键词
palmitic acid; albumin; growth hormone; liver; fatty acid binding protein; uptake; hepatic; long-chain fatty acids; clofibrate; hypophysectomy;
D O I
10.1139/cjpp-77-11-896
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 [H-3]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 [H-3]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 mu M albumin, hepatocyte clearance rates of unbound [H-3]palmitate from hypophysectomized animals (0.16 +/- 0.01 and 0.64 +/- 0.01 mL.s(-1).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.s(-1).10(-6) cells, respectively). However, the unbound [H-3]palmitate clearance rates from the clofibrate-treated group (0.39 +/- 0.04 and 1.18 +/- 0.12 mL.s(-1).10(-6) cells) were significantly higher (p < 0.01) than the control group (0.29 +/- 0.02 and 0.81 +/- 0.05 mL.s(-1).10(-6) cells) for 2 and 20 mu M 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 mu M/CL2 mu M. 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.
引用
收藏
页码:896 / 901
页数:6
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