Fatty acid-binding proteins - Insights from genetic manipulations

Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC, Canada V5A 1S6.
Progress in Lipid Research (Impact Factor: 10.02). 08/2004; 43(4):328-49. DOI: 10.1016/j.plipres.2004.05.001
Source: PubMed


Fatty acid-binding proteins (FABPs) belong to the conserved multigene family of the intracellular lipid-binding proteins (iLBPs). These proteins are ubiquitously expressed in vertebrate tissues, with distinct expression patterns for the individual FABPs. Various functions have been proposed for these proteins, including the promotion of cellular uptake and transport of fatty acids, the targeting of fatty acids to specific metabolic pathways, and the participation in the regulation of gene expression and cell growth. Novel genetic tools that have become available in recent years, such as transgenic cell lines, animals, and knock-out mice, have provided the opportunity to test these concepts in physiological settings. Such studies have helped to define essential cellular functions of individual FABP-types or of combinations of several different FABPs. The deletion of particular FABP genes, however, has not led to gross phenotypical changes, most likely because of compensatory overexpression of other members of the iLBP gene family, or even of unrelated fatty acid transport proteins. This review summarizes the properties of the various FABPs expressed in mammalian tissues, and discusses the transgenic and ablation studies carried out to date in a functional context.

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Available from: Norbert Haunerland, Jul 02, 2014
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    • "The main difference between the two structures is that nanoKAZ has an insertion region including the a4-helix and b4-strand, which are missing in hFABP5 (Fig. 4A). The FABP family is known as lipid-binding proteins with molecular masses around 15 kDa, and FABPs can bind long-chain fatty acids, bile acids or retinoids[30]. The ligand in FABP is noncovalently bound in the internal cavity and is almost inaccessible to the solvent[31]. "
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    ABSTRACT: The 19 kDa protein (KAZ) of Oplophorus luciferase is a catalytic component, that oxidizes coelenterazine (a luciferin) with molecular oxygen to emit light. The crystal structure of the mutated 19 kDa protein (nanoKAZ) was determined at 1.71 Å resolution. The structure consists of 11 antiparallel β-strands forming a β-barrel that is capped by 4 short α-helices. The structure of nanoKAZ is similar to those of fatty acid-binding proteins (FABPs), even though the amino acid sequence similarity was very low between them. The coelenterazine-binding site and the catalytic site for the luminescence reaction might be in a central cavity of the β-barrel structure.
    Full-text · Article · Dec 2015 · Biochemical and Biophysical Research Communications
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    • "However, the divergent sequences of the members confer subtle differences in their ligand-binding properties and may also indicate different protein–protein interaction partners depending on the cellular context. Indeed, it has been shown that intracellular adipocyte-, epithelial-, and heart-type FABPs interact with hormone-sensitive lipase , whereas the intestinal and liver isoforms do not [3] [4] [5] [6] [7]. It is also known that FABP4 interacts with Janus Kinase 2 in a fatty aciddependent manner, establishing a new role for FABP4 as a fatty acid sensor that affects cellular metabolism via protein–protein interactions [8]. "
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    ABSTRACT: Fatty acid-binding protein 4 (FABP4) is an adipose tissue-secreted adipokine that is involved in the regulation of energetic metabolism and inflammation. Increased levels of circulating FABP4 have been detected in individuals with cardiovascular risk factors. Recent studies have demonstrated that FABP4 has a direct effect on peripheral tissues, specifically promoting vascular dysfunction; however, its mechanism of action is unknown. The objective of this work was to assess the specific interactions between exogenous FABP4 and the plasma membranes of endothelial cells. Immunofluorescence assays showed that exogenous FABP4 localized along the plasma membranes of human umbilical vein endothelial cells (HUVECs), interacting specifically with plasma membrane proteins. Anti-FABP4 immunoblotting revealed two covalent protein complexes containing FABP4 and its putative receptor; these complexes were approximately 108 kDa and 77 kDa in size. Proteomics and mass spectrometry experiments revealed that cytokeratin 1 (CK1) was the FABP4-binding protein. An anti-CK1 immunoblot confirmed the presence of CK1. FABP4-CK1 complexes were also detected in HAECs, HCASMCs, HepG2 cells and THP-1 cells. Pharmacological FABP4 inhibition by BMS309403 results in a slight decrease in the formation of these complexes, indicating that fatty acids may play a role in FABP4 functionality. In addition, we demonstrated that exogenous FABP4 crosses the plasma membrane to enter the cytoplasm and nucleus in HUVECs. These findings indicate that exogenous FABP4 interacts with plasma membrane proteins, specifically CK1. These data contribute to our current knowledge regarding the mechanism of action of circulating FABP4.
    Full-text · Article · Sep 2015 · Biochimica et Biophysica Acta
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    • "IFABP has not been found to be involved with chylomicron formation [35] [57]; hence, IFABP has been proposed to be involved with uptake of FA from the lumen of the intestine, and with trafficking within the intestinal enterocyte to organelles [34]. It is also thought that both FABPs may serve as a cytosolic reservoir for FA required for various cellular functions, while also preventing accumulation of unesterified FA, which are known to modify membrane properties [4]. IFABP is typical among the members of the FABP family in that it has a single site where its FA ligand is bound. "
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    ABSTRACT: Fatty acid-binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both liver- (LFABP; FABP1) and intestinal FABPs (IFABP; FABP2) are expressed. These proteins display high-affinity binding for long-chain fatty acids (FA) and other hydrophobic ligands; thus, they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand-binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have different functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte.
    Full-text · Article · Oct 2014 · Prostaglandins Leukotrienes and Essential Fatty Acids
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