Induction of hepatic cytosolic fatty acid binding protein with clofibrate accelerates both membrane and cytoplasmic transport of palmitate.
The role of liver cytosolic fatty acid binding protein (L-FABP) in fatty acid transport and metabolism is unclear. Female liver contains substantially more L-FABP than male liver. Female liver also has a different fatty acid transport phenotype, including more rapid uptake, efflux and cytoplasmic transport. However, it is not known if the greater levels of L-FABP are responsible for these differences. We therefore determined whether increasing L-FABP using clofibrate causes male liver to acquire a female transport phenotype. The multiple indicator dilution (MID) method was used to estimate the rate constants for influx, efflux and cytoplasmic diffusion of palmitate in isolated perfused rat livers. Clofibrate treatment increased cytosolic concentrations of L-FABP 4.2+/-0.8-fold, the rate of cytoplasmic diffusion of palmitate 4.3+/-1.7-fold, and the steady-state palmitate extraction 1.5+/-0.3-fold (mean+/-S.E.). Influx and efflux constants were both increased (by 44% and 79%, respectively) to levels typical of female livers. These data suggest that clofibrate-induced elevation of cytosolic L-FABP not only stimulates intracellular diffusion but also influx and efflux of fatty acids. Possible mechanisms include reducing fatty acid binding to cytoplasmic membranes, induction of membrane fatty acid carriers, and catalyzing fatty acid exchange between aqueous cytoplasm and the plasma membrane.
Luxon
B A
BA
Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Louis University Health Sciences Center, St. Louis, MO, USA.
Milliano
M T
MT
Weisiger
R A
RA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000096:biosynthesis*; D002462:Cell Membrane / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004058:Diffusion; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008956:Models, Chemical; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010168:Palmitates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic; D013395:Sucrose / Q000378:metabolism; D014316:Tritium; D015854:Up-Regulation
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; C493320:Fabp1 protein, mouse; C493321:Fabp1 protein, rat; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D000960:Hypolipidemic Agents; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010168:Palmitates; D014316:Tritium; D013395:Sucrose; D002994:Clofibrate