Liver type fatty acid binding protein (L-FABP) directly interacts with peroxisome proliferator-activated receptor-alpha  in cultured primary hepatocytes

doi:10.1194/jlr.M900058-JLR200

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A more recent version of this article appeared on August 1, 2009

Papers In Press, published online ahead of print March 16, 2009
J. Lipid Res., doi:10.1194/jlr.M900058-JLR200

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Submitted on February 9, 2009
Revised on March 12, 2009
Accepted on March 16, 2009

Liver type fatty acid binding protein (L-FABP) directly interacts with peroxisome proliferator-activated receptor- $alpha$ in cultured primary hepatocytes

Heather A. Hostetler, Avery L. McIntosh, Barbara P. Atshaves, Stephen M. Storey, H. Ross Payne, Ann B. Kier, and Friedhelm Schroeder

Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466

Corresponding Author: fschroeder{at}cvm.tamu.edu

Although studies with liver type fatty acid binding protein (L-FABP) gene ablated mice demonstrate a physiological role for L-FABP in hepatic fatty acid metabolism, little is known about the mechanism(s) whereby L-FABP elicits these effects. Such studies indicate that L-FABP may function to shuttle lipids to the nucleus, thereby increasing the availability of ligands of nuclear receptors, such as peroxisome proliferator-activated receptor- $alpha$ (PPAR $alpha$ ). The data herein suggest that such mechanisms involve direct interaction of L-FABP with PPAR $alpha$ . L-FABP was shown to directly interact with PPAR $alpha$ in vitro through co-immunoprecipitation of pure proteins, altered circular dichroic spectra, and altered fluorescence spectra. Furthermore, in vitro fluorescence resonance energy transfer (FRET) between Cy3-labeled PPAR $alpha$ and Cy5-labeled L-FABP proteins showed that these proteins bound with high affinity (Kd ~156nM) and in close proximity (intermolecular distance of 52Å). This interaction was further substantiated by co-immunoprecipitation of both proteins from liver homogenates of wild type mice. Moreover, double immunogold electron microscopy and double immunofluorescence energy transfer (FRET) confocal microscopy of cultured primary hepatocytes showed that L-FABP was in close proximity to PPAR $alpha$ (intermolecular distance 40-49Å) in vivo. Taken together, these studies were consistent with L-FABP regulating PPAR $alpha$ transcriptional activity in hepatocytes through direct interaction with PPAR $alpha$ .

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[Abstract] [Full Text] [PDF]

Liver type fatty acid binding protein (L-FABP) directly interacts with peroxisome proliferator-activated receptor- in cultured primary hepatocytes

Liver type fatty acid binding protein (L-FABP) directly interacts with peroxisome proliferator-activated receptor- $alpha$ in cultured primary hepatocytes