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Journal of Lipid Research, Vol. 47, 665-672, March 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Fatty acid transport protein 1 and long-chain acyl coenzyme A synthetase 1 interact in adipocytes

M. Rachel Richards, Jeffrey D. Harp, Daniel S. Ory and Jean E. Schaffer¹

Center for Cardiovascular Research and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110

Published, JLR Papers in Press, December 15, 2005.

¹ To whom correspondence should be addressed. e-mail: jschaff{at}wustl.edu

The fatty acid transport proteins (FATP) and long-chain acyl coenzyme A synthetase (ACSL) proteins have been shown to play a role in facilitating long-chain fatty acid (LCFA) transport in mammalian cells under physiologic conditions. The involvement of both FATP and ACSL proteins is consistent with the model of vectorial acylation, in which fatty acid transport is coupled to esterification. This study was undertaken to determine whether the functions of these proteins are coordinated through a protein-protein interaction that might serve as a point of regulation for cellular fatty acid transport. We demonstrate for the first time that FATP1 and ACSL1 coimmunoprecipitate in 3T3-L1 adipocytes, indicating that these proteins form an oligomeric complex. The efficiency of FATP1 and ACSL1 coimmunoprecipitation is unaltered by acute insulin treatment, which stimulates fatty acid uptake, or by treatment with isoproterenol, which decreases fatty acid uptake and stimulates lipolysis. Moreover, inhibition of ACSL1 activity in adipocytes impairs fatty acid uptake, suggesting that esterification is essential for fatty acid transport. Together, our findings suggest that a constitutive interaction between FATP1 and ACSL1 contributes to the efficient cellular uptake of LCFAs in adipocytes through vectorial acylation.

Supplementary key words oligomer • fatty acid transport protein • ACSL • lipid import

Abbreviations: ACSL, long-chain acyl coenzyme A synthetase; FATP, fatty acid transport protein; HRP, horseradish peroxidase; LCFA, long-chain fatty acid

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