Tissue-specific Functions in the Fatty Acid-binding Protein Family

Department of Nutritional Sciences and the Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 10/2010; 285(43):32679-83. DOI: 10.1074/jbc.R110.135210
Source: PubMed


The intracellular fatty acid-binding proteins (FABPs) are abundantly expressed in almost all tissues. They exhibit high affinity
binding of a single long-chain fatty acid, with the exception of liver FABP, which binds two fatty acids or other hydrophobic
molecules. FABPs have highly similar tertiary structures consisting of a 10-stranded antiparallel β-barrel and an N-terminal
helix-turn-helix motif. Research emerging in the last decade has suggested that FABPs have tissue-specific functions that
reflect tissue-specific aspects of lipid and fatty acid metabolism. Proposed roles for FABPs include assimilation of dietary
lipids in the intestine, targeting of liver lipids to catabolic and anabolic pathways, regulation of lipid storage and lipid-mediated
gene expression in adipose tissue and macrophages, fatty acid targeting to β-oxidation pathways in muscle, and maintenance
of phospholipid membranes in neural tissues. The regulation of these diverse processes is accompanied by the expression of
different and sometimes multiple FABPs in these tissues and may be driven by protein-protein and protein-membrane interactions.

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    • "The importance of this last metamorphosis phase would explain why cluster D, the second largest, also included brain fatty acidbinding proteins that promote fatty acid uptake and target specific pathways and the regulation of gene expression. Highly expressed in all tissues they reflect tissue-specific aspects of fatty acid metabolism; their up-regulation is likely related to the early proliferation/differentiation of neural stem cells[63,64]. Thus, they mediate the transport and activity of long chain PUFAs, essential for brain development and functions, including the generation of neuronal and/or glial cells, differentiation , neurone migration and axis patterning[63,65]. "

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    • "Moreover, the expression profile of FABPs in cerebral cortex confirms that FABP5 and 7 were expressed in the brain mainly at the late embryonic stage [23] with an abundance level 10-times higher than that of other fatty acid transport proteins. This superiority , which persists until day 14 of lactation, is supposed to be required during brain development for AA and DHA channelling for phospholipid and membrane synthesis during proliferation/ differentiation of stem cells and neurite outgrowth [23] [49]. "
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    • "These proteins are widely distributed throughout the body; they have distinct tissue distributions and exhibit a different degree of binding promiscuity. Due to their central role in lipid-mediated biological processes and systemic metabolic homeostasis [7] [8], iLBPs have been proposed as therapeutic targets against lipid-related disorders. "
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    ABSTRACT: Lipids are essential for many biological processes and crucial in the pathogenesis of several diseases. Intracellular lipid-binding proteins (iLBPs) provide mobile hydrophobic binding sites that allow hydrophobic or amphipathic lipid molecules to penetrate into and across aqueous layers. Thus iLBPs mediate the lipid transport within the cell and participate to a spectrum of tissue-specific pathways involved in lipid homeostasis. Structural studies have shown that iLBPs binding sites are inaccessible from the bulk, implying that substrate binding should involve a conformational change able to produce a ligand entry portal. Many studies have been reported in the last two decades on iLBPs indicating that their dynamics play a pivotal role in regulating ligand binding and targeted release. The ensemble of reported data has not been reviewed until today. This review is thus intended to summarise and possibly generalise the results up to now described, providing a picture which could help to identify the missing notions necessary to improve our understanding of the role of dynamics in iLBPs molecular recognition. Such notions would clarify the chemistry of lipid binding to iLBPs and set the basis for the development of new drugs.
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