Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites

2003 ◽  
Vol 284 (3) ◽  
pp. G423-G433 ◽  
Author(s):  
Daniel Y. Hung ◽  
Frank J. Burczynski ◽  
Ping Chang ◽  
Andrew Lewis ◽  
Paul P. Masci ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Low Molecular Weight ◽  
Metabolic Clearance ◽  
Pharmacokinetic Models ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Rat Livers

Disposition kinetics of [3H]palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [3H]palmitate and its low-molecular-weight metabolites, and several physiologically based pharmacokinetic models. The level of liver fatty acid binding protein (L-FABP), other intrahepatic binding proteins (microsomal protein, albumin, and glutathione S-transferase) and the outflow profiles of [3H]palmitate and metabolites were measured in four experimental groups of rats: 1) males; 2) clofibrate-treated males; 3) females; and 4) pregnant females. A slow-diffusion/bound model was found to better describe the hepatic disposition of unchanged [3H]palmitate than other pharmacokinetic models. The L-FABP levels followed the order: pregnant female > clofibrate-treated male > female > male. Levels of other intrahepatic proteins did not differ significantly. The hepatic extraction ratio and mean transit time for unchanged palmitate, as well as the production of low-molecular-weight metabolites of palmitate and their retention in the liver, increased with increasing L-FABP levels. Palmitate metabolic clearance, permeability-surface area product, retention of palmitate by the liver, and cytoplasmic diffusion constant for unchanged [3H]palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [3H]palmitate and its low-molecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins.

Reduced hepatic extraction of palmitate in steatosis correlated to lower level of liver fatty acid binding protein

2005 ◽  
Vol 288 (1) ◽  
pp. G93-G100 ◽  
Author(s):  
Daniel Y. Hung ◽  
Gerhard A. Siebert ◽  
Ping Chang ◽  
Frank J. Burczynski ◽  
Michael S. Roberts
Keyword(s):  
Molecular Weight ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Pharmacokinetic Analysis ◽  
Low Molecular Weight ◽  
Liver Fatty Acid ◽  
Hepatic Extraction ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Nonalcoholic fatty liver disease is the most common of all liver diseases. The hepatic disposition [3H]palmitate and its low-molecular-weight metabolites in perfused normal and steatotic rat liver were studied using the multiple indicator dilution technique and a physiologically based slow diffusion/bound pharmacokinetic model. The steatotic rat model was established by administration of 17α-ethynylestradiol to female Wistar rats. Serum biochemistry markers and histology of treated and normal animals were assessed and indicated the presence of steatosis in the treatment group. The steatotic group showed a significantly higher alanine aminotransferase-to-aspartate aminotransferase ratio, lower levels of liver fatty acid binding protein and cytochrome P-450, as well as microvesicular steatosis with an enlargement of sinusoidal space. Hepatic extraction for unchanged [3H]palmitate and production of low-molecular-weight metabolites were found to be significantly decreased in steatotic animals. Pharmacokinetic analysis suggested that the reduced extraction and sequestration for palmitate and its metabolites was mainly attributed to a reduction in liver fatty acid binding protein in steatosis.

Heart-type fatty acid-binding protein reciprocally regulates glucose and fatty acid utilization during exercise

2005 ◽  
Vol 288 (2) ◽  
pp. E292-E297 ◽  
Author(s):  
Jane Shearer ◽  
Patrick T. Fueger ◽  
Jeffrey N. Rottman ◽  
Deanna P. Bracy ◽  
Bert Binas ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Whole Body ◽  
Metabolic Clearance ◽  
Fatty Acid Binding ◽  
Nonesterified Fatty Acids ◽  
Acid Binding Protein

The role of heart-type cytosolic fatty acid-binding protein (H-FABP) in mediating whole body and muscle-specific long-chain fatty acid (LCFA) and glucose utilization was examined using exercise as a phenotyping tool. Catheters were chronically implanted in a carotid artery and jugular vein of wild-type (WT, n = 8), heterozygous (H-FABP+/−, n = 8), and null (H-FABP−/−, n = 7) chow-fed C57BL/6J mice, and mice were allowed to recover for 7 days. After a 5-h fast, conscious, unrestrained mice were studied during 30 min of treadmill exercise (0.6 mph). A bolus of [125I]-15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid and 2-deoxy-[3H]glucose was administered to obtain rates of whole body metabolic clearance (MCR) and indexes of muscle LCFA (Rf) and glucose (Rg) utilization. Fasting, nonesterified fatty acids (mM) were elevated in H-FABP−/− mice (2.2 ± 0.9 vs. 1.3 ± 0.1 and 1.3 ± 0.2 for WT and H-FABP+/−). During exercise, blood glucose (mM) increased in WT (11.7 ± 0.8) and H-FABP+/− (12.6 ± 0.9) mice, whereas H-FABP−/− mice developed overt hypoglycemia (4.8 ± 0.8). Examination of tissue-specific and whole body glucose and LCFA utilization demonstrated a dependency on H-FABP with exercise in all tissues examined. Reductions in H-FABP led to decreasing exercise-stimulated Rf and increasing Rg with the most pronounced effects in heart and soleus muscle. Similar results were seen for MCR with decreasing LCFA and increasing glucose clearance with declining levels of H-FABP. These results show that, in vivo, H-FABP has reciprocal effects on glucose and LCFA utilization and whole body fuel homeostasis when metabolic demands are elevated by exercise.

Calcium-dependent release of adipocyte fatty acid binding protein from human adipocytes

2014 ◽  
Vol 122 (03) ◽  
Author(s):  
I Schlottmann ◽  
M Ehrhart-Bornstein ◽  
M Wabitsch ◽  
SR Bornstein ◽  
V Lamounier-Zepter
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Human Adipocytes ◽  
Fatty Acid Binding ◽  
Calcium Dependent ◽  
Acid Binding Protein

Biochemical and Histochemical Studies of Liver Fatty Acid Binding Protein in Alcohol-Treated Rats.

1993 ◽  
Vol 14 (3) ◽  
pp. 171-181
Author(s):  
Shigeya WATANABE ◽  
Yoshio WAKATSUKI ◽  
Hideyuki YOSHIOKA ◽  
Masami INADA ◽  
Teruo ONO ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Liver Fatty Acid ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Diagnostic value of fatty acid-binding protein determination in urologists and nephrologists clinical practice

2020 ◽  
pp. 92-99
Author(s):  
Konstantin R. Galkovich
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Physiological Role ◽  
Diagnostic Value ◽  
Obstructive Nephropathy ◽  
Malignant Neoplasms ◽  
Early Screening ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

This review summarizes the data on the diagnostic value of determining the fatty acid-binding protein (FABP) in urological and nephrological diseases. A physiological role of this protein in the pathogenesis of malignant neoplasms of the kidney, bladder, and prostate was analyzed. The dynamics of FABP in serum and urine with decreased renal function was studied: this protein is considered as a diagnostic and prognostic marker for chronic kidney disease and acute renal injury. The value of FABP for early screening of patients with obstructive nephropathy was revealed, and its role in predicting the restoration of kidney function was studied: the dynamics of FABP content can characterize the process of graft recovery, determine the need for hemodialysis. In patients with oligozooastenospermia, a reduced content of FABP in the ejaculate was registered, which was probably an adverse sign indicating a violation of male fertility.

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