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 ac id 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 tr ansport. However, it is not known if the greater levels of L-FABP are respo nsible for these differences. We therefore determined whether increasing L- FABP using clofibrate causes male liver to acquire a female transport pheno type. The multiple indicator dilution (MID) method was used to estimate the rate constants for influx, efflux and cytoplasmic diffusion of palmitate i n isolated perfused rat livers. Clofibrate treatment increased cytosolic co ncentrations 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 incre ased (by 44% and 79%, respectively) to levels typical of female livers. The se data suggest that clofibrate-induced elevation of cytosolic L-FABP not o nly stimulates intracellular diffusion but also influx and efflux of fatty acids. Possible mechanisms include reducing fatty acid binding to cytoplasm ic membranes, induction of membrane fatty acid carriers, and catalyzing fat ty acid exchange between aqueous cytoplasm and the plasma membrane. (C) 200 0 Elsevier Science B.V. All rights reserved.