The Role of Intracellular Fatty Acid-Binding Proteins in Cellular Transport of Fatty Acids

Abstract

The family of mammalian fatty acid-binding proteins (FABP) includes at least ten distinct gene products, and additional homologues continue to be reported. The FABP were first discovered in the early 1970’s as abundant cytoplasmic proteins which bound long chain fatty acids (FA) in vitro 11-3. In the ensuing years, a great deal of information has been obtained about their tissue distributions, ligand binding affinities and specificities, developmental regulation and, more recently, their tertiary structures 3-5 Their functions, however, remain largely undefined. Among the first members of the FABP family to be purified were those from intestine 1,6, liver 1,2 and heart7. In all these tissues, fatty acid flux is considerable, and thus it was proposed that the FABP are necessary for large-scale intracellular binding of fatty acids. More recently, FABP family members have been identified in other tissues that are generally considered to be lipid-active, e.g. adipose tissue 8, as well as other tissues, e.g. brain 9,10. In addition, the FABP have been suggested as modulators not only of lipid metabolism and cellular FA flux, but also of gene expression, cell growth and differentiation, etc.11-13 It is also of interest that a number of cell types, most notably intestinal enterocytes, express high and approximately equivalent levels of two separate FABP’s 14 suggesting a functional specificity for different family members. In all of these tissues and for all of these putative functions, a role for FABP in cytoplasmic transport of FA from sites of entry and/or synthesis to sites of utilization and function, is implied.